Podcasts about aacr

睽違半年Happy Hour總算更新啦！這次若晴跟Angel來聊聊最近剛從研討會回來的一些見聞和心得，非常適合搭配上一集新手村005一起收聽！當然我們也不忘Happy Hour的慣例，跟大家分享了一則近期非常振奮人心的客製化基因療法突破的新聞。等待Happy Hour已久的聽眾趕緊收聽吧！ 節目內容： 跟大家更新一下近況 客製化基因療法大突破 芝加哥三腳貓4/6小聚 AACR開幕式小花絮 跟同事學了poster session的搜集資訊的招數 小廢物拿好拿滿還有免費專業大頭照 NIH fellowship小會議見聞 會議結識新朋友的喜悅 -- Hosting provided by SoundOn

“The thing that I worry about more than loss of exclusivity is this term that I introduced at the AACR meeting -- loss of relevancy" says Susan Galbraith, EVP of Oncology R&D at AstraZeneca. In this episode, Galbraith and David Fredrickson, EVP of Oncology Business Unit, join Bloomberg Intelligence analyst Sam Fazeli fresh from ASCO to discuss how AstraZeneca is navigating an increasingly complex oncology landscape. From a legacy in small molecules to a bold push into areas ranging from cell therapy to antibody-drug conjugates, they explain how the company aims to sustain growth and relevance. The discussion also covers new trial designs, biomarker-driven strategies, and why innovation, not exclusivity, is the true metric of success.See omnystudio.com/listener for privacy information.

June 10, 2025 | In this bonus episode of The Chain, Daniel Chen, MD, PhD, founder and CEO of Synthetic Design Lab, returns for the Science Commune segment and speaks with Keith Flaherty, MD, FAACR, professor of Medicine of Harvard Medical School and president-elect of AACR. They discuss Flaherty's prolific career; how his background led him to pursue a career in medicine; how public and private sectors are coming together in oncology around collaborations; reflections on targeted therapies and technologies; optimism around how AI will impact society and the future of medicine positively; and how we need to detect and treat disease early. Links from this episode:  PEGS Boston Conference & Expo Engineering Bispecific Antibodies Synthetic Design Lab Harvard Medical School AACR 

I sit down with Marina Udier, CEO of Nouscom, a Swiss company working on the Lynch Syndrome vaccine.  Nous209 is designed to intercept tumors in Lynch Syndrome cancers.  The 209 comes from the frameshifts of neoantigens, whether sporadic or hereditary.  Idea is to educate the T-cells before cancers start forming.  The data at AACR presented was very promising.  They are also running a study on metastatic colorectal cancer patients, mostly without Lynch Syndrome, but MSI high.  So how many people are tested positive for Lynch Syndrome each year?  Next steps includes additional investigators and patients for a much bigger trial, at a time to be determined, and of course funding is always a priority.  Suffice it so say, interest is high is seeing this come to late stage development.    

The exact origins of SARS-CoV-2 are still something of a mystery, but new research may bring scientists one step closer to an explanation for how the virus reached Wuhan. Also in the episode, we dive into GEN's coverage of the annual AACR meeting including how the community is navigating massive research budget cuts. Then we discuss a potential colorectal cancer therapy using CRISPR-edited tumor infiltrating lymphocytes and a method for delivering protein therapies and gene editors using engineered vesicles. Lastly, in business news, Recursion rethinks its pipeline, the FDA gives Abeona's gene therapy a chance, and Bristol Myers Squibb execs open up on artificial intelligence.Join GEN editors Corinna Singleman, PhD, Alex Philippidis, Julianna LeMieux, PhD, and Uduak Thomas for a discussion of the latest biotech and biopharma news. Listed below are links to the GEN stories referenced in this episode of Touching Base:AACR 2025: A Video Update from ChicagoBy Julianna LeMieux, PhD and Damian Doherty, GEN, April 29, 2025Hope and Headwinds at AACR in ChicagoBy Damian Doherty, GEN, April 29, 2025Senator Tammy Baldwin Supports Science in AACR SpeechBy Julianna LeMieux, PhD, GEN, April 29, 2025CRISPR-Edited TILs Fight Advanced Colorectal Cancer in PatientsBy GEN, May 4, 2025Engineered Extracellular Vesicles Could Deliver Gene Editors, Therapeutic Proteins to CellsBy GEN, April 30, 2025SARS-CoV-2 Likely Spread Through Wildlife Trade, Not Bat MigrationBy GEN, May 7, 2025Chatting with Author David Quammen about SARS-CoV-2 Will Leave You “Breathless”Originally aired: November 16, 2022Recursion Halts Four Pipeline Programs, Sharpening Cancer, Rare Disease FocusBy Alex Philippidis, GEN Edge, May 5, 2025StockWatch: Second Time's the Charm for Abeona's Gene TherapyBy Alex Philippidis, GEN Edge, May 4, 2025Predict First: BMS Executives Discuss Company's AI ApproachBy Alex Philippidis, GEN Edge, March 26, 2025 Hosted on Acast. See acast.com/privacy for more information.

Tonix Pharmaceuticals Holdings CEO Dr Seth Lederman joined Steve Darling from Proactive to share encouraging preclinical results presented at the American Association for Cancer Research, highlighting the company's novel therapeutic candidate TNX-1700 for gastric cancer. In the study, a murine fusion protein (mTFF2-MSA) was tested, modeling the human fusion version TFF2-HSA currently under development as TNX-1700. Dr. Lederman explained that combining mTFF2-MSA with anti-PD1 immunotherapy significantly reduced tumor immunosuppression in animal models. Specifically, the therapy decreased immunosuppressive neutrophils and cancer-induced granulopoiesis, while stimulating CD8+ T-cell responses that helped inhibit tumor progression. The study also revealed a negative correlation between TFF2 expression and PMN-MDSC levels in gastric cancer patients, supporting the clinical relevance of TFF2 modulation in immuno-oncology. Tonix plans to continue advancing TNX-1700 as a first-in-class fusion protein therapeutic for hard-to-treat cancers. #proactiveinvestors #tonixpharmaceuticalsholdingcorp #nasdaq #tnxp #Biotech #TonixPharmaceuticals #TNX1700 #GastricCancer #CancerResearch #Immunotherapy #PD1Blockers #AACR2025 #BiotechNews #OncologyInnovation #CancerTreatment

In today's episode, supported by Revolution Medicines, we spoke with Kathryn C. Arbour, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, about 2 important abstracts presented at the 2024 AACR Annual Meeting that explore novel RAS-targeted approaches in non–small cell lung cancer (NSCLC). Our discussion focused on early clinical findings with zoldonrasib (RMC-9805) and daraxonrasib (RMC-6236), both of which are RAS(ON) inhibitors under investigation for the treatment of patients with RAS-mutant NSCLC. Zoldonrasib, a KRAS G12D-selective tri-complex inhibitor, was evaluated in a phase 1 trial (NCT06040541) in patients with previously treated, advanced KRAS G12D–mutated solid tumors, including NSCLC. Daraxonrasib, a multi-selective RAS(ON) inhibitor, was highlighted in another phase 1 trial (NCT05379985) in patients with advanced RAS-mutant tumors, including previously treated NSCLC; notably, this AACR presentation focused on the association between early on-treatment circulating tumor DNA level reduction and clinical response with the agent. In this episode, Dr Arbour shared insights into the mechanisms of action behind these therapies, their respective clinical trial designs, and the potential implications that early data with the agents may have for the evolving RAS-mutant NSCLC treatment paradigm.

On this week's episode, Eric Schmidt and Sam Fazeli are joined by special guests Adam Feuerstein and Peter Kolchinsky to discuss the upward movement of the biotech market along with strong drug launches, deals, and net-positive Q1 earnings, all signaling things may be improving. Next, the group notes the FDA is unlikely to undergo significant reorganization and while this stability is reassuring, complacency should be avoided as headwinds persist. Despite the turmoil, the pharmaceutical industry remains resilient, as people prioritize their health and the need for medicine. The conversation shifts back to the new FDA leadership, highlighting Makary and RFK Jr.'s relationship, anti-vaccine rhetoric and the impacts this may have on vaccine trials. The group notes that at conversations at AACR suggest that large pharma is not worried about the FDA changes, while smaller companies have concerns. BridgeBio's successful launch of Attruby was also discussed, highlighted as a positive trend for the industry. The conversation shifts back to vaccine uncertainty and the future of mRNA given the skepticism from healthcare professionals, illustrated by Moderna's potential delays fortheir flu vaccine combo. The episode ends with Adam's optimistic take on biotech's recent turn toward stabilization. *This episode aired on May 2, 2025.

Among the formerly undruggable targets gaining translational momentum, SMARCA2 has intrigued researchers for its potential to treat challenging solid tumors. On the latest BioCentury This Week podcast, BioCentury's editors zero in on preclinical research supporting different degraders of SMARCA2 at this year's American Association for Cancer Research (AACR) annual meeting.They also discuss takeaways from Editor in Chief Simone Fishburn's conversation with David Baker, the Nobel-prizewinning pioneer in protein design, and Steve Usdin reports that pharmaceutical industry executives are in a state of alarm over President Trump's push to include a “most favored nation” policy for Medicaid drug purchases in budget reconciliation legislation. Usdin also discusses why industry executives are confident of a fix for the Inflation Reduction Act's “pill penalty” and FDA Commissioner Marty Makary's decision to reject proposals to reorganize the agency. This episode was sponsored by Jeito Capital.View full story: https://www.biocentury.com/article/655851#biotech #biopharma #pharma #LifeScience #RandD #DrugDevelopment #AACR #SMARCA200:01 - Sponsor Message: Jeito Capital03:01 - AACR Spotlight11:21 - David Baker Protein Design19:12 - Trump's Drug Pricing PlanTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Two companies, Beam Therapeutics and Verve Therapeutics, have developed lead candidates using a safer alternative to conventional CRISPR called base editing. Clinical results have been promising. FDA insiders are calling on FDA Commissioner Marty Makary to fight against agency politicization. The Trump administration, including HHS Secretary Robert F. Kennedy Jr., is accused of distorting and denying scientific truths and potentially censoring information.FDA action alerts include expansion bids for drugs by GSK and Merck. A new AI-powered solution called Generative AIPTP helps life sciences firms streamline clinical workflows. The FDA is rehiring travel staff as lapses begin to show.RFK Jr. is driving a wedge into vaccine conversations. WHO may add obesity drugs for adults to the essential medicines list. Various companies like Merck, GSK, and Roche present key data at AACR 2025.HHS will require placebo-controlled trials for all new vaccines in a radical departure from past practices. Tariffs dominate Q1 earnings, AACR excites the cancer space, CEO pay gaps are discussed, and more news and events are highlighted.

AACR 2025 Highlights by IASLC

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Novartis recently acquired Regulus for $1.7 billion, signaling a trend of increased M&A activity in the pharmaceutical industry. Many companies have hinted at upcoming deals during recent earnings calls, which is seen as a positive sign for the biopharma ecosystem amidst challenges like tariffs and potential drug pricing pressures. GSK remains optimistic about M&A opportunities despite the threat of tariffs, with CEO Emma Walmsley emphasizing a cautious and disciplined approach to dealmaking. Trilink Biotechnologies has introduced custom sets of mRNA for screening studies, offering flexibility and scalability for research needs. The AACR 2025 conference featured promising data from Marengo and Briacell, while Pfizer CEO Albert Bourla has been lobbying against pharmaceutical industry tariffs proposed by President Trump. Overall, the industry is seeing a mix of challenges and opportunities, with companies navigating trade tensions and economic uncertainties while also pursuing strategic growth through acquisitions and innovative research initiatives.Pharmaceutical companies are navigating political uncertainties, particularly in relation to tariffs and dealmaking with China. Major companies are investing billions in US manufacturing to avoid tariffs threatened by President Trump. Despite lobbying efforts, Trump has expressed national security concerns regarding the pharmaceutical industry. CEO-to-employee pay gaps in the industry remain significant. Novartis, GSK, and AstraZeneca are facing challenges and making strategic shifts in response to political and market conditions. Tariff uncertainty is impacting Q1 earnings, with companies like Merck taking significant financial hits. Despite these challenges, the industry remains active with mergers and acquisitions. Upcoming events and job opportunities in the biopharma sector are highlighted.

Policy issues—particularly tariffs—loom large as Q1 2025 earnings season rolls on, with Pfizer , Novartis, AstraZeneca and many more all reporting this week. On Pfizer's call, CEO Albert Bourla called the Trump administration's national security concerns “legitimate,” but objected to the proposed tariffs in general. Meanwhile, Novartis CEO Vas Narasimhan brushed off the tariff risk but expressed concern over President Donald Trump's desire to bring back the ‘Most Favored Nations' rule.  Meanwhile, cancer conference season is in full swing, with the American Association for Cancer Research's annual event continuing in Chicago. Merck, GSK, Boehringer Ingelheim, Roche and others have presented highly anticipated data from some of their cornerstone cancer drugs and other candidates.  Turning to the latest news out of the FDA, newly minted Commissioner Marty Makary gave his first two big press interviews last week, making statements that both jibed with and contradicted recent reporting. And in the midst of the ongoing Novavax vaccine saga, many have raised concerns that the FDA could become politicized under the watch of HHS Secretary RFK Jr.  Finally, check out this week's BioPharm Executive stories, including a deep dive into the trend toward mining innovative therapies from China and BioSpace's annual report on pharma CEO-to-employee pay ratios. 

Biopharma companies are vying to dethrone Vyvgart as a leading therapy for myasthenia gravis, with the latest data for therapies treating the rare autoimmune neuromuscular disease coming at this month's American Academy of Neurology. On a special episode of the BioCentury This Week podcast, BioCentury's editors discuss the landscape for MG therapies, including anti-BLyS and APRIL therapy telitacicept from Remegen. Joining BioCentury's editors are Qing Zuraw, chief development officer of podcast sponsor RemeGen, and Amit Sachdev, PI on global trials of the biotech's therapy. BioCentury's editors also preview the American Association for Cancer Research annual meeting, where degraders and bispecifics are defining translational trends at this year's event. This episode of BioCentury This Week podcast was sponsored by RemeGen.View full story: https://www.biocentury.com/article/655751#biotech #biopharma #pharma #lifescience #AAN #AACR00:01 - Sponsor Message: RemeGen Co.01:02 - Myasthenia Gravis at AAN08:31 - RemeGen's Telitacicept18:03 - AACR: Targets and TrendsTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

Loss of leadership, cuts to staffing and a proposed reorganization at FDA have heightened biotech risk amid an already turbulent macroeconomic climate, according to BioCentury's Washington editor Steve Usdin. On the latest BioCentury This Week podcast, BioCentury's editors discuss how the turmoil at FDA could affect a sector already grappling with the uncertainty brought by the Trump administration's trade war.The editors also explore the growing pipeline of VEGF-targeted bispecifics in a preview of upcoming presentations at annual meeting for the American Association for Cancer Research (AACR). And they discuss how companies may once again need to lean on their bear market survival toolkit, as part of BioCentury's 2Q25 Financial Markets Preview. This episode of BioCentury This Week was sponsored by RemeGen Co.View full story: https://www.biocentury.com/article/65556600:01 - Sponsor Message: RemeGen Co. 01:19 - FDA and Tariffs Turmoil16:54 - AACR Preview20:44 - Bear Market ToolkitTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

In this special episode, I sit down with Ricki Fairley of TOUCH, The Black Breast Cancer Alliance and Hayley Dinerman of the Triple Negative Breast Cancer Foundation to discuss the latest advancements in TNBC research, including key takeaways from SABCS 2024, new immunotherapy and targeted therapies, and the impact of the AACR research grant. We also explore efforts to address racial disparities, upcoming awareness initiatives, and how you can get involved. Don't miss this insightful conversation about the future of TNBC treatment and advocacy. Thank you to Merck, Daiichi-Sankyo, Gilead, Pfizer, and Lilly for making this episode possible!  

JCO PO author Dr. David R. Gandara at UC Davis Comprehensive Cancer Center, shares insights into his JCO PO article, “Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer,” one of the Top Articles of 2024. Host Dr. Rafeh Naqash and Dr. Gandara discuss how the PROphet® blood test supports first-line immunotherapy treatment decisions for metastatic NSCLC patients. TRANSCRIPT  Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we bring you engaging conversations with authors of clinically relevant and highly significant JCOPO articles. I'm your host, Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma.  Today, we are absolutely thrilled to be joined by Dr. David R. Gandara, Professor of Medicine Emeritus, Co-Director of the Center for Experimental Therapeutics and Cancer and Senior Advisor to the Director at UC Davis Comprehensive Cancer Center and also the senior author of the JCO Precision Oncology article entitled “Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer.” This was one of the top performing articles of 2024, which is one of the reasons why we wanted to bring it in for a podcast discussion. At the time of this recording, our guest's disclosures will be linked in the transcript.  David, it is an absolute pleasure to have you today. For somebody like you who's led the field of lung cancer over the years, I'm really excited that you are going to be talking to us about this very interesting article, especially given that I think you're one of the big proponents of liquid biopsies and plasma-based testing. So, for the sake of our listeners - which comprises of academic oncologists, community oncologists, trainees - could you tell us where the biomarker landscape for non-small cell lung cancer is currently, and then we can try to take a deeper dive into this article. Dr. David Gandar: Okay. Well, thank you, Rafeh. It's a pleasure to be with you here today. And I think the current landscape for biomarkers for immunotherapy in non-small cell lung cancer is a mess. There's no better way to describe it. That makes this paper describing a new plasma proteomic assay even more important. So I'll just give you a perspective. There are 14 trials, phase three trials, that were done in first line non-small cell lung cancer advanced stage of immunotherapy versus chemotherapy and some other aspects, although they vary tremendously. Some of them were checkpoint monotherapy, some combined with chemotherapy, some combined with CTLA-4 inhibitors and so forth. 12 out of the 14 were positive, 12 got FDA approval. So there are 12 different options that an oncologist could use. Some of them were squamous cell only, some non-squamous, some used PD-L1 as a biomarker driven part of the study. Some used TMB, tumor mutational burden, some were agnostic. So when you put all of this together, an oncologist can pick and choose among all these various regimens. And by and large, it's PD-L1 that is the therapeutic decision maker.  ASCO actually, I think, has done the very best job of making a guideline, and it's, as you well know, called a living guideline, it's dynamic. And it is much easier to interpret, for me and I think for oncologists, than some of the other guidelines. It's got a green light and a red light, it may be kind of orange. And so the green light means this is a strong recommendation by the guideline committee. The orange means it's weak. For this purpose, non-small cell lung cancer, advanced stage, only a very few of the recommendations were green. It's mainly monotherapy and patients with cancers with a PD-L1 over 50%. In our surveys, at our meetings, less than 50% of oncologists in the United States are following these guidelines. Why? Because they don't trust the biomarker. And TMB has the same sort of limitations. They're not bad biomarkers, they're incomplete. They're only looking at a part of the story. So that means we need a new biomarker. And this is one that, I think, the data are quite impressive and we'll discuss it more. Dr. Rafeh Naqash: Absolutely. Like you said, abundance of many therapy options, but not necessarily everything works the same in different subsets of PD-L1 positivity or different subsets of patients with different levels of tumor burden. And like you said, again, difficulty in trying to identify the right biomarker. And that's a nice segue to this PROphet test that you guys ran. So can you tell us a little bit about the plasma proteomic assay? Because to the best of my knowledge, there's not a lot of validated plasma proteomic assays. A lot has been done on the tumor tissue side as far as biomarkers are concerned, but not much on the blood side, except for maybe ctDNA MRD testing. So what was the background for trying to develop a plasma-based proteomic test? And then how did this idea of testing it in the lung cancer setting come into play? And then we can go into the patient population specifics, the cohort that you guys have. Dr. David Gandara: Okay. Well, of course there's a company behind this assay, it's called OncoHost, and I'm a consultant for them. And they came to me two years ago and they said, “We have something different from anyone else.” And they explained the science to me, as well as some other lung cancer experts here in the United States. I'm not a proteomic expert, of course, but they developed an AI machine learning platform to assess plasma proteins in normal people and in people with cancer, and specifically then in people with non-small cell lung cancer. They identified over 7,000 proteins that had cancer implications for therapy, for resistance, for prognosis, etc., and they categorized them based on the literature, TCGA data, etc., and used this machine learning process to figure out which proteins might be most specific for non-small cell lung cancer. And that's where they started. And so out of that 7,000 proteins, where they've identified which ones are angiogenic, which ones are involved with EMT or cell cycle or whatever it might be, they distilled it down to 388 proteins which they thought were worth testing in non-small cell lung cancer. And that's when I became involved.  They had a retrospective cohort of patients that had been treated with various immunotherapies. They looked at the analytic validation first, then applied it to this cohort. It looked good. Then they had a very large cohort, which they split, as you usually do with an assay, into a test set and then a validation set. For the test set, they wanted something more than a response. They wanted some indicator of long term benefit because that's where immunotherapy differentiates itself from chemotherapy and even targeted therapy. And so they picked PFS at 12 months. And I became involved at that point and it looked really good. I mean, if you look at the figures in the manuscript, the AUC is superb about their prediction and then what actually happened in the patient. And then in this paper, we applied it to a validation set of over 500 patients in a prospective trial, not randomized, it's called an observational trial. The investigator got to pick what they thought was the best therapy for that patient. And then in a blinded fashion, the proteomic assay experts did the analysis and applied it to the group.  And so what that means is some of the patients got chemotherapy alone, some got checkpoint immunotherapy monotherapy, some got in combination with chemotherapy. None of the patients in this study got a CTLA-4 inhibitor. That work is ongoing now. But what the study showed was that this assay can be used together with PD-L1 as what I would call a composite biomarker. You take the two together and it informs the oncologist about the meaning of that PD-L1. I'll give you an example. If that patient has a PD-L1 over 50% in their cancer and yet the PROphet test is negative, meaning less than 5 - it's a 0 to 10 scale - that patient for survival is better served by getting chemotherapy and immunotherapy. However, if the PROphet test is positive and the PD-L1 is over 50%, then the survival curves really look equivalent. As I said earlier, even in that group of patients, a lot of oncologists are reluctant to give them monotherapy. So if you have a test and the same sort of example is true for PD-L1 0, that you can differentiate. So this can really help inform the oncologist about what direction to go. And of course then you use your clinical judgment, you look at what you think of as the aggressiveness of the tumor or their liver metastases, etc. So again, that's how this test is being used for non-small cell lung cancer. And maybe I'll stop there and then I'll come back and add some other points. Dr. Rafeh Naqash: I definitely like your analogy of this therapy de-escalation strategy. Like you mentioned for PD-L1 high where the PROphet test is negative, then perhaps you could just go with immunotherapy alone. In fact, interestingly enough, I was invited to a talk at SITC a couple of weeks back and this exact figure that you're referring to was one of the figures in my slide deck. And it happened by chance that I realized that we were doing a podcast on the same paper today.  So I guess from a provocative question standpoint, when you look at the PD-L1 high cohort in the subset where you didn't see a survival difference for chemo plus immunotherapy versus immunotherapy alone, do you think any element of that could have been influenced by the degree of PD-L1 positivity above 50%? Meaning could there have been a cohort that is, let's say PD-L1 75 and above, and that kind of skews the data because I know you've published on this yourself also where the higher the PD-L1 above 50%, like 90% PD-L1 positivity survival curves are much better than 50% to 89%. So could that have somehow played a role? Dr. David Gandara: The first thing to say is that PD-L1 and the PROphet score, there's very little overlap. I know that sounds surprising, but it's also true for tumor mutational burden. There's very little overlap. They're measuring different things. The PD-L1 is measuring a specific regulatory protein that is applicable to some patients, but not all. That's why even in almost all of the studies, people with PD-L1 0 could still have some survival benefit. But in this case they're independent. And not in this paper, but in other work done by this group, the PROphet group, they've shown that the PROphet score does not seem to correlate with super high PD-L1. So it's not like the cemiplimab data where if you have a PD-L1 of greater than 90%, then of course the patient does spectacularly with monotherapy. The other thing that's important here is they had a group of around a little less than 100 patients that got chemotherapy alone. The PROphet score is agnostic to chemotherapy. And so that means that you're not just looking at some prognostic factor. It's actually clinical utility on a predictive basis. Dr. Rafeh Naqash: I think those are very important points. I was on a podcast a couple of days back. I think there's a theme these days we're trying to do for JCO Precision Oncology, we're trying to do a few biomarker based podcasts, and the most recent one that we did was using a tissue transcriptome with ctDNA MRD and you mentioned the composite of the PD-L1 and the PROphet test and they use a composite of the tissue transcriptome. I believe they called it the VIGex test as well as MRD ctDNA. And when your ctDNA was negative at, I believe, the three month mark, those individuals had the highest inflamed VIGex test or highest infiltration of T cells, STING pathway, etc. So are there any thoughts of trying to add or correlate tissue based biomarkers or ctDNA based correlations as a further validation in this research with the company? Dr. David Gandara: Right. So there are many things that are being looked at, various composites looking at the commutations that might affect the efficacy of immunotherapy and how they correlate with profit positivity or negativity. And I'll just give the examples of STK11 and KEAP1. As you know, there's some controversy about whether these are for immunotherapy, whether they're more prognostic or predictive. I'm one of the co-authors among many in the recently published Nature paper by Dr. Skoulidis and the group at MD Anderson which report that for KEAP1 positive especially, but also SDK11 mutated getting immunotherapy, that that's where the CTLA-4 inhibitors actually play the greatest role. So realizing that this is still controversial, there are preliminary data, not published yet, that'll be presented at an upcoming meeting, looking at many of these other aspects, P53, SCK11, KEAP1, other aspects, TMB, that's actually already published, I think in one of their papers. So yes, there's lots of opportunities.  The other cool thing is that this isn't a test, it's a platform. And so that means that the OncoHost scientists have already said, “What if we look at this test, the assay in a group of patients with small cell lung cancer?” And so I just presented this as a poster at the world conference in San Diego. And it turns out if you look at the biology of small cell, where neither PD-L1 nor TMB seem to be very important, if you look at the biology of small cell and you form an assay, it only shares 44 proteins out of the 388 with non-small cell. It's a different biology. And when we applied that to a group of patients with small cell lung cancer, again it had really pretty impressive results, although still a fairly small number of patients. So we have a big phase three study that we're doing with a pharmaceutical company developing immunotherapy where we are prospectively placing the PROphet test in a small cell trial.  The platform can also be altered for other cancer types. And at AACR, Dr. Jarushka Naidoo presented really impressive data that you can modify the proteins and you can predict immunotherapy side effects. So this is not like a company that says, “We have one test that's great for everything.” You know how some companies say, “Our test, you can use it for everything.” This company is saying we can alter the protein structures using AI machine learning assisted process to do it and we can have a very informed assay in different tumor types and different situations. So to me, it's really exciting. Dr. Rafeh Naqash: Definitely to me, I think, combining the AI machine learning aspect with the possibility of finding or trying to find a composite biomarker using less invasive approaches such as plasma or blood, definitely checks a lot of boxes. And as you mentioned, trying to get it to prospective trials as an integral biomarker perhaps would be likely the next step. And hopefully we see some interesting, exciting results where we can try to match or stratify patients into optimal combination therapies based on this test.  So now to the next aspect of this discussion, David, which I'm really excited about. You've been a leader and a mentor to many. You've led ISLC and several other corporate group organizations, et cetera. Can you tell us, for the sake of all the listeners, junior investigators, trainees, what being a mentor has meant for you? How your career has started many years back and how it's evolved? And what are some of the things that you want to tell people for a successful and a more exciting career as you've led over the years? Dr. David Gandara: Well, thank you for the question. Mentoring is a very important part of my own career. I didn't have an institutional mentor when I was a junior investigator, but I had a lot of senior collaborators, very famous people that kind of took me under their wing and guided me. And I thought when I basically establish myself, I want to give back by being a mentor to other people. And you wouldn't believe the number of people that I'm even mentoring today. And some of them are not medical oncologists, they're surgeons, they're radiation oncologists, they're basic scientists. Because you don't have to be an expert in that person's field to be a mentor. It helps, but in other words, you can guide somebody in what are the decision making processes in your career. When is it time to move from this institution onward because you can't grow in the institution you're in, either because it's too big or it's too small? So I established a leadership academy in the Southwest Oncology Group, SWOG. I've led many mentoring courses, for instance, for ISLC, now for International Society Liquid Biopsy, where I'm the executive committee liaison for what's called The Young Committee. So ISLB Society, totally devoted to liquid biopsy, six years old now, we have a Young Committee that has a budget. They develop projects, they publish articles on their own, they do podcasts. So what I'm saying is those are all things that I think opens up opportunities. They're not waiting behind senior people, they are leading themselves.  We just, at our International Lung Cancer Congress, reestablished a fellows program where a group of fellows are invited to that Huntington beach meeting. It's now in its 25th year and we spend a day and a half with them, mentoring them on career building. I'll just give you my first, I have the “Letterman Top 10”. So my first recommendation is if all you have is lemons, make lemonade. And what I'm meaning is find what you can do at your institution if you're a junior person, what you can claim to be your own and make the very best of it. But then as you get further along in my recommendations, one of them is learn when to say ‘no'. Because as a junior investigator the biggest threat to your career is saying ‘yes' to everybody and then you become overwhelmed and you can't concentrate. So I'll stop there. But anyway, yes, mentoring is a big part of my life. Dr. Rafeh Naqash: Well, thank you, David. This is definitely something that I'm going to try to apply to my career as well. And this has been an absolute pleasure, especially with all the insights that you provided, not just on the scientific side but also on the personal career side and the mentorship side. And hopefully we'll see more of this work that you and other investigators have led and collaborated on. perhaps more interesting plasma based biomarkers. And hopefully some of that work will find its home in JCO Precision Oncology. Thank you again for joining us today. Dr. David Gandara: My pleasure. Dr. Rafeh Naqash: And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service organization, activity or therapy should not be construed as an ASCO endorsement.   Dr. David Gandara Disclosures: Consulting or Advisory Role Company: Henlius USA, Foundation Medicine, Janssen Pharma, Merck & Co, Mirati Therapeutics, Regeneron, AstraZeneca, Guardant Health, Genentech, Exact Sciences  Research Funding Company: Amgen, Genentech, Astex Pharma  

Send us a textMichael J. Burton is the CEO of the Diabetes Research Institute Foundation ( https://diabetesresearch.org/ ), a philanthropic organization which funds the Diabetes Research Institute, one of the largest and most comprehensive research centers dedicated to curing diabetes.A passionate nonprofit executive, Michael has more than 30 years of experience in leading high-impact philanthropic programs and cultivating strategic relationships to secure transformative funding. Prior to assuming the role of CEO at DRIF, Michael advanced the missions of some of the nation's most dynamic and trusted institutions including Princeton University, The Pew Charitable Trusts and the American Association for Cancer Research (AACR).Michael's accomplished nonprofit career includes significant contributions in the advancement of cancer research and care, most recently as President and CEO of Gateway for Cancer Research, a Chicago-based nonprofit engaged in funding early phase clinical research, where he began his tenure as Chief Development Officer. Prior to that, Michael served as Chief Development Officer and Executive Director of the Foundation at the AACR, the nation's oldest and largest organization dedicated to the prevention and cure of all cancers. Michael's 15 years of experience in the oncology sector also includes leading the development program at Fox Chase Cancer Center as Senior Vice President and Chief Development Officer.Before working in the field of oncology, Michael had a distinguished career in higher education, most notably at the University of Pennsylvania, where he served as Special Assistant to the President during the tenure of Judith Rodin, the first female president of an Ivy League institution; and at Temple University, where he held the title of Assistant Dean and lead the development program at the Fox School of Business. Before entering higher education, Michael served as Legislative and Press Assistant to the late Congressman Tom Lantos, the only survivor of the Holocaust ever elected to Congress. Michael is a graduate of the University of Pennsylvania, where he earned a Bachelor's degree in Communications and a Master's degree in Public Administration. Prof. Dr. Matthias von Herrath, MD is the Scientific Director of the Diabetes Research Institute (DRI) and Stacy Joy Goodman Chair at the University of Miami School of Medicine ( https://med.miami.edu/faculty/matthias-georg-von-herrath ) where he is leading the DRI mission to conduct and accelerate research to delay, prevent and ultimately find a cure for type 1 diabetes.  He is widely recognized for his groundbreaking work in understanding the molecular mechanisms of T1D, an autoimmune disease in which the body's immune system attacks and destroys insulin-producing beta cells in the pancreas, and developing novel therapies for this disease. Prof. Dr. von Herrath served as a Professor and Director for the Type 1 Diabetes Research Center at La Jolla Institute for Allergy and Immunology, and also currently serves as Vice President and Senior Medical Officer at Novo Nordisk, a global healthcare company, where he is responsible for overseeing the company's research and development efforts in diabetes care.Prof. Dr. von Herrath earned his medical degree in 1988 from Freiburg Medical School, where he also completed a Ph.D. equivalent thesis on biochemistry. His postdoctoral training included an intensive care residency at Diakonie Hospital, Freiburg.#DiabetesResearchInstituteFoundation #T1D #Insulin #IsletCellTransplant #Regeneration #Immunomodulation #Immunoregulation #Autoimmune #UniversityOfMiami #Philanthropy #NovoNordisk #Instacart  #ProgressPotentialAndPossibilities #IraPastor #PodcSupport the show

Dr. Vivek Subbiah returns for another edition of Vivek's Takes, sharing his insights on key updates from ESMO Congress 2024, including breakthroughs in neuroendocrine tumors, gastric cancer, and non-small cell lung cancer. He also delves into the highlights of his AACR debate on integrating early cancer detection with AI, arguing for the transformative potential of humans with AI versus the readiness of AI today. Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on YouTube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

Perry Marshall is a world-renowned business strategist, celebrated for his expertise in applying the 80/20 Principle to transform businesses from seven-figure revenue to eight figures. Endorsed by FORBES and INC Magazine, Perry is one of the most expensive and influential consultants. He has authored ten books, including the acclaimed Ultimate Guide to Google Ads, which laid the foundations for the $500 billion digital advertising industry. Perry's reinvention of the Pareto Principle is featured in Harvard Business Review. NASA's Jet Propulsion Labs uses his 80/20 Curve for productivity. He founded the $10 million Evolution 2.0 Prize, announced at London's Royal Society, the world's largest science research challenge. Perry is a co-founder of the AACR's Cancer & Evolution Working Group. Based in Chicago with his family, Perry's influence extends across over 300 industries. Listen to this informative Sharkpreneur episode with Perry Marshall about the 80/20 sales and marketing revolution. Here are some of the beneficial topics covered on this week's show: - How the 80/20 rule is a universal principle applicable beyond business. - Why you shouldn't rely on quick-fix tactics that eventually become obsolete. - How asking deeper questions and pursuing curiosity unlocks new insights. - Why the best scientists maintain their curiosity and humanity. - How meaningful connections and insights can emerge from following your passions. Connect with Perry: Guest Contact Info X: @PerryMarshall Facebook: facebook.com/perrymarshallcom Links Mentioned: https://www.perrymarshall.com/ Learn more about your ad choices. Visit megaphone.fm/adchoices

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-396 Overview: Listen in as we discuss the health risks of e-cigarette use and dual use, emphasizing the importance of primary prevention and supporting patients in their cessation efforts. Discover the latest evidence on vaping's impact on addiction, cardiovascular health, and lung cancer, and gain essential insights to better advise your patients. Episode resource links: Bittoni MA, et al. Abstract 2213. Presented at: American Association for Cancer Research Annual Meeting; April 5-10, 2024; San Diego. (AACR 2024: Ohio State experts share new findings at annual meeting (press release). Available at: https://cancer.osu.edu/news/aacr-2024-ohio-state-experts-share-new-findings. Posted April 5,2024. Accessed May 3, 2024.) Hartmann-Boyce J, McRobbie H, Lindson N, et al. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. Apr 29 2021;4:CD010216. doi:10.1002/14651858.CD010216.pub5 Hopkinson NS, et al "Association of time spent on social media with youth cigarette smoking and e-cigarette use in the UK: a national longitudinal study" Thorax 2024: DOI:10.1136/ thorax-2023-220569. Y.W. Kim, E.J. Park, K.I. Kwak, A.-R. Choi, B.J. Lee, Y.J. Lee, J.S. Park, Y.-J. Cho, J.H. Lee, and C.-T. Lee. Association of Electronic Cigarette Use After Conventional Smoking Cessation With Lung Cancer Risk: A Nationwide Cohort Study (abstract). Am J Respir Crit Care Med 2024;209:A3051. CDC: Health Effects of Vaping; https://www.cdc.gov/tobacco/e-cigarettes/health-effects.html CDC:Dual Use of Tobacco Products; https://www.cdc.gov/tobacco/campaign/tips/diseases/dual-tobacco-use.html Guest: Susan Feeney, DNP, FNP-BC, NP-C  Music Credit: Richard Onorato Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-396 Overview: Listen in as we discuss the health risks of e-cigarette use and dual use, emphasizing the importance of primary prevention and supporting patients in their cessation efforts. Discover the latest evidence on vaping's impact on addiction, cardiovascular health, and lung cancer, and gain essential insights to better advise your patients. Episode resource links: Bittoni MA, et al. Abstract 2213. Presented at: American Association for Cancer Research Annual Meeting; April 5-10, 2024; San Diego. (AACR 2024: Ohio State experts share new findings at annual meeting (press release). Available at: https://cancer.osu.edu/news/aacr-2024-ohio-state-experts-share-new-findings. Posted April 5,2024. Accessed May 3, 2024.) Hartmann-Boyce J, McRobbie H, Lindson N, et al. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. Apr 29 2021;4:CD010216. doi:10.1002/14651858.CD010216.pub5 Hopkinson NS, et al "Association of time spent on social media with youth cigarette smoking and e-cigarette use in the UK: a national longitudinal study" Thorax 2024: DOI:10.1136/ thorax-2023-220569. Y.W. Kim, E.J. Park, K.I. Kwak, A.-R. Choi, B.J. Lee, Y.J. Lee, J.S. Park, Y.-J. Cho, J.H. Lee, and C.-T. Lee. Association of Electronic Cigarette Use After Conventional Smoking Cessation With Lung Cancer Risk: A Nationwide Cohort Study (abstract). Am J Respir Crit Care Med 2024;209:A3051. CDC: Health Effects of Vaping; https://www.cdc.gov/tobacco/e-cigarettes/health-effects.html CDC:Dual Use of Tobacco Products; https://www.cdc.gov/tobacco/campaign/tips/diseases/dual-tobacco-use.html Guest: Susan Feeney, DNP, FNP-BC, NP-C  Music Credit: Richard Onorato Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com  

Elizabeth Jaffee, MD, is an internationally recognized expert in cancer immunology and pancreatic cancer. She is the Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Co-director of the Skip Viragh Center for Pancreatic Cancer and Associate Director of the Bloomberg Kimmel Institute for Cancer Immunotherapy. Her research focuses on developing novel immunotherapies for the treatment and prevention of pancreatic cancer. Dr. Jaffee is a past president of AACR. She has served on a number of committees at the National Cancer Institute including the Co-chair of the Biden Moonshot Blue Ribbon Panel which identified high research priorities for the NCI. “You can be an amazing scientist, but what's most important is that whatever you do in science has implications for the patient.” From being inspired by Dr. Marie Curie's biography as a child to now becoming one of the leading names in pancreatic cancer research internationally, Dr. Elizabeth Jaffee helps us re-focus on the patient and our role as ‘physician' scientists. Tune in to this episode of The Medicine Mentors as we journey with Dr. Jaffee to connect the science with the patient. Pearls of Wisdom:   1. Regardless of the direction we take in our professional journey, we have to keep the implications of our actions and research focused on our patients and how we can help them. 2. While leadership is a forefront activity and mentorship an educational activity, both can be thought of as similar in that you're helping someone become the best version of themselves. That means taking into account each individual's strengths and weaknesses and tailoring that to the intended outcome. 3. Don't have just one mentor. It's futile hoping that one person can teach you everything you'll need to know. Find a network of individuals that can help you, which starts by putting yourself out there as someone who wants to do more and wants help.  

Dr. Hahn is the William Rosenberg Professor of Medicine in the Department of Medical Oncology at Dana-Farber Cancer Institute and Harvard Medical School and an Institute Member of the Broad Institute of MIT and Harvard. He serves as an Executive Vice President and the Chief Operating Officer at the Dana-Farber Cancer Institute. Dr. Hahn has made numerous discoveries that have informed our currentmolecular understanding of cancer. His laboratory has pioneered the use of integrated functional genomic approaches to identify and validate cancer targets. The tools, models and approaches that his laboratory has developed are widely used worldwide to discover and validate molecularly targeted cancer therapies. Dr. Hahn has served as the President of the American Society for ClinicalInvestigation and has been elected to the Association of American Physicians and the National Academy of Medicine. Dr. Hahn has been the recipient of many honors and awards including the Wilson S. Stone Award from M.D. Anderson Cancer Center for outstanding research in cancer (2000), a Howard Temin Award from the National Cancer Institute (2001), the Ho-Am Prize in Medicine (2010), the Richard and Hinda Rosenthal Award from AACR (2015) and the Claire and Richard Morse Award (2019). He has been elected to the American Society of Clinical Investigation, American Association of Physicians, the National Academy of Inventors and the National Academy of Medicine.

We've seen tremendous progress in diagnosing and treating cancer, but not all people have benefited from that progress equally. The American Association for Cancer Research recently released their 2024 Cancer Disparities Progress Report, which highlights gaps in diagnoses, treatment, and outcomes for people in marginalized groups. What is being done to close those gaps? We talk with Mitch Stoller, Chief Philanthropic Officer and Vice President of Development for the AACR, and Dr. Camille Ragin, a professor and Associate Director of Diversity, Equity, and Inclusion at Fox Chase Cancer Center and a member of the steering committee for the AACR's report. And on Shara in the City, we get ready for the first year of Olympic breakdancing by visiting Philly's longest-running hip-hop and breakdancing event, The Gathering at The Rotunda. To learn more about listener data and our privacy practices visit: https://www.audacyinc.com/privacy-policy Learn more about your ad choices. Visit https://podcastchoices.com/adchoices

In this weeks episode, we will have the part two of Dr Barrie Tan's episode. The information you will learn from todays episode - if you take it onboard, will indeed change your life, longevity and health for the better so this is a must listen to podcast with actionable insights and incredible clinical research behind it. What you will learn:  Who is Dr. Barrie Tan?. What is Vitamin E - Tocotrienol? What is GG? What is the difference between tocotrienol and GG?  What is the difference between tocotrienol and tocopherol? Which annatto should you take? What is the link between CoQ10 and statins and GG. What is the link between GG and testosterone? Why should you take MK-4 and GG?... Tocotrienols roles in bone density Tocotrienols roles in Non alcoholic fatty liver disease, pre diabetes, diabetes, cardiovascular disease Tocotrienols role in fighting various cancer types GG's role in bone density, muscle synthesis, coenzyme Q10 absorption and much much more. website  https://barrietan.com/ Riverside Nutrition his manufacturing company - The research mentioned in this show is available at https://americanrivernutrition.com/ If you want to get GG, Tocotrienols or Coqnol (Coenzyme Q10 with GG), you can reach us out directly through our email support@lisatamati.com and we can organize that. BIO A scientist first and foremost, Dr. Tan earned his Ph.D. in chemistry/biochemistry from the University of Otago, New Zealand, and spent several years as a professor at UMass. Dr. Tan has committed himself to the research and development of phytonutrients — natural compounds found in plants that reduce and slow chronic disorders. Dr. Barrie Tan is hailed as a trailblazer and the world's foremost expert on vitamin E, credited with discovering tocotrienol in three major natural sources and geranylgeraniol, an essential nutrient with implications for sports and active nutrition. A scientist first and foremost, Dr. Tan earned his Ph.D. in Chemistry/Biochemistry from the University of Otago, New Zealand and spent several years as a professor at UMass. Today, his research focuses on lipid-soluble nutrients that reduce and slow chronic conditions. Dr. Tan is credited with discovering a form of vitamin E called tocotrienol from three major sources: palm, rice, and annatto — a natural dye and food coloring derived from the seeds of the achiote tree, known for its potential health benefits, including antioxidant and antimicrobial properties. Editor of two prestigious books on tocotrienol and founder of the International Tocotrienol Conference, Dr. Tan was dubbed the "Tocotrienol King" by Dr. Stephen Sinatra, a highly respected and sought-after cardiologist. Dr. Tan has held roles of Chief Scientific Officer and Scientific Board Member for multinational organizations. His career includes periods working in association with the US Armed Forces and a Prince of Thailand. He has successfully launched multiple businesses in the nutrition industry and owns an array of patents and intellectual property, keeping him at the forefront of scientific innovation. He is an internationally celebrated and sought-after speaker, having presented at multiple respected conferences in the field including; IFT, ADA, ASN, IHS, A4M, NPA, AACR, ICIM, IAOMT, and the Academy of Nutrition and Dietetics. Dr. Tan is currently the President of American River Nutrition, a natural health R&D company he started with his wife, Elizabeth, in 1998. Described as a scientific pioneer, his mission is simple: improve the everyday health of people's lives through the rigorous application of DeltaGold® – the first-ever tocopherol-free tocotrienol product extracted from annatto, and the most potent form of vitamin E in existence today. As for links, we'd love to give people a free copy of his eBook The Truth About Vitamin E which can be found at https://barrietan.com/book/ using code: Pushing The Limits   Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

In this weeks episode, world renown Vitamin E researcher and also GG researcher, author and founder of American River Nutrition is today's illustrious guest, Dr Barrie Tan. The information you will learn from todays episode - if you take it onboard, will indeed change your life, longevity and health for the better so this is a must listen to podcast with actionable insights and incredible clinical research behind it. What you will learn:  Who is Dr. Barrie Tan?. What is Vitamin E - Tocotrienol? What is GG? What is the difference between tocotrienol and GG?  What is the difference between tocotrienol and tocopherol? Which annatto should you take? What is the link between CoQ10 and statins and GG. What is the link between GG and testosterone? Why should you take MK-4 and GG?... Tocotrienols roles in bone density Tocotrienols roles in Non alcoholic fatty liver disease, pre diabetes, diabetes, cardiovascular disease Tocotrienols role in fighting various cancer types GG's role in bone density, muscle synthesis, coenzyme Q10 absorption and much much more. website  https://barrietan.com/ Riverside Nutrition his manufacturing company - The research mentioned in this show is available at https://americanrivernutrition.com/ If you want to get GG, Tocotrienols or Coqnol (Coenzyme Q10 with GG), you can reach us out directly through our email support@lisatamati.com and we can organize that. BIO A scientist first and foremost, Dr. Tan earned his Ph.D. in chemistry/biochemistry from the University of Otago, New Zealand, and spent several years as a professor at UMass. Dr. Tan has committed himself to the research and development of phytonutrients — natural compounds found in plants that reduce and slow chronic disorders. Dr. Barrie Tan is hailed as a trailblazer and the world's foremost expert on vitamin E, credited with discovering tocotrienol in three major natural sources and geranylgeraniol, an essential nutrient with implications for sports and active nutrition. A scientist first and foremost, Dr. Tan earned his Ph.D. in Chemistry/Biochemistry from the University of Otago, New Zealand and spent several years as a professor at UMass. Today, his research focuses on lipid-soluble nutrients that reduce and slow chronic conditions. Dr. Tan is credited with discovering a form of vitamin E called tocotrienol from three major sources: palm, rice, and annatto — a natural dye and food coloring derived from the seeds of the achiote tree, known for its potential health benefits, including antioxidant and antimicrobial properties. Editor of two prestigious books on tocotrienol and founder of the International Tocotrienol Conference, Dr. Tan was dubbed the "Tocotrienol King" by Dr. Stephen Sinatra, a highly respected and sought-after cardiologist. Dr. Tan has held roles of Chief Scientific Officer and Scientific Board Member for multinational organizations. His career includes periods working in association with the US Armed Forces and a Prince of Thailand. He has successfully launched multiple businesses in the nutrition industry and owns an array of patents and intellectual property, keeping him at the forefront of scientific innovation. He is an internationally celebrated and sought-after speaker, having presented at multiple respected conferences in the field including; IFT, ADA, ASN, IHS, A4M, NPA, AACR, ICIM, IAOMT, and the Academy of Nutrition and Dietetics. Dr. Tan is currently the President of American River Nutrition, a natural health R&D company he started with his wife, Elizabeth, in 1998. Described as a scientific pioneer, his mission is simple: improve the everyday health of people's lives through the rigorous application of DeltaGold® – the first-ever tocopherol-free tocotrienol product extracted from annatto, and the most potent form of vitamin E in existence today. As for links, we'd love to give people a free copy of his eBook The Truth About Vitamin E which can be found at https://barrietan.com/book/ using code: Pushing The Limits   Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

In today's episode of Beating Cancer Daily, Saranne takes us on an exhilarating journey to the annual AACR convention, a gathering of the world's leading oncological researchers committed to eradicating cancer. As a Stage IV cancer conqueror with no visible disease, she highlights the cutting-edge advancements and personal triumphs reverberating through the halls of this inspiring event. Saranne's perspective as a survivor, researcher, and patient advocate shines a light on how vital patient input is in the search for the next big breakthrough. Dive in as she discusses how anyone touched by cancer can leverage the AACR resources to become more involved, from learning about the latest research to supporting clinical trials. Let's harness the shared hope and collective effort to beat cancer daily.The #1 Rated Cancer Survivor Podcast by FeedSpot and Ranked Top 5 Best Cancer Podcast by CancerCare News. Beating Cancer Daily is listened to in over 77 countries on 6 continents and has over 260 daily episodes!  In 1999, Saranne launched The ComedyCures Foundation from her chemo chair with a "Chemo Comedy Party." Now cancer-free, she's dedicated her life to helping others find strength, courage, and laughter in their fight against cancer. As a healthcare thought leader, speaker, patient advocate, and health and happiness expert, Saranne's work has garnered recognition and support from prestigious organizations like the NIH/NCI, the United Nations, the World Health Organization, and numerous universities and cancer societies. Saranne's transformative strategies, research findings, fun, practical tips, and comic insights can be found in the "Beating Cancer Daily" podcast and the BCD Membership Circle, where she helps listeners navigate their treatment and survivorship with humor and resilience. Are you wondering How You Can Support Beating Cancer Daily and ComedyCures.org?By becoming a supporter of ComedyCures.org, you'll help us continue our essential programs and research. Your generosity will significantly impact cancer patients, caregivers, doctors, nurses, and researchers worldwide. Choose your level of support:• Supporter: $50 (or $5 per month)• Friend: $150 (or $15 per month)• Champion: $500 (or $50 per month)• VIP: $5,000 annually Donate Herehttps://www.paypal.com/donate?hosted_button_id=GDPQCM8PHJT We Share the Laughter with Beating Cancer Daily Podcast Do you love the podcast? Please share it with a friend and spread the laughter!  

A combination of a new mRNA vaccine used together with a programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor to treat patients with lung cancer was markedly less toxic than a combination of the same vaccine with chemotherapy. However, it was apparently just effective. This is according to findings from a study reported to the 2024 AACR Annual Meeting. The randomized study, led by the researchers at the Moffitt Cancer Center, looked at a combination of the mRNA-based active cancer vaccine BI1361849 combined with the anti-PD-L1 checkpoint inhibitor durvalumab with or without the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitor tremelimumab immunotherapy. After announcing the findings at the AACR, presenting author Dung-Tsa Chen, PhD, Senior Member in the Department of Biostatistics & Informatics, Special Clinical Trial Design, and Data Analysis at the Moffitt Cancer Center, called in to discuss the new data with OncTimesTalk correspondent Peter Goodwin.

The 2024 AACR Annual Meeting heard that an “efficacy signal” was detected in an international Phase I study of a new radiosensitizer, tested as adjunctive therapy (combined with standard radiation plus temozolomide) in patients with recurrent glioblastoma. After reporting his group's early findings of AZD1390, an inhibitor of ataxia telangiectasia mutated (ATM) kinase studied in 115 patients with recurrent or newly diagnosed glioblastoma, first author Jonathan T. Yang MD, PhD, previously from the Memorial Sloan Kettering Cancer Center and now at UW Medicine, stepped into the Oncology Times studio at the AACR conference to tell OncTimesTalk's reporter Peter Goodwin about the safety of this new agent and the clinical value it could bring in glioblastoma.

A new blood test that uses artificial intelligence to analyze circulating molecular markers for the earliest signs of ovarian and other cancers has been reported by researchers. At the AACR 2024 Annual Meeting in San Diego, Victor Velculescu, MD, PhD, Co-Director of the Cancer Genetics & Epigenetics Program at Johns Hopkins Kimmel Cancer Center, reported his group's validation of the test that assesses the pattern of circulating fragments of tumor DNA, known as fragmentomes. After discussing the findings at an AACR press briefing, Velculescu joined Peter Goodwin in the OncTimesTalk podcast studio to discuss the clinical implications.

An early study using selective inhibition of the Poly (ADP-ribose) polymerase (PARP) has provided evidence it could bring greater cancer control with less toxicity than the well-proven non-selective PARP 1 and PARP 2 inhibitors already in use for treating a number of tumor types. At the AACR Annual Meeting 2024, Timothy Yap, PhD, MD, MBBS, Vice President and Head of Clinical Development in the Therapeutics Discovery Division at the University of Texas MD Anderson Cancer Center, reported early data from the PETRA study looking at the selective PARP 1 inhibitor saruparib under investigation as a potentially safer, yet more effective, alternative to the non-selective PARP 1/PARP 2 inhibitors currently licensed for prostate, ovarian, breast, and other cancers. After announcing the new research findings at a clinical session at AACR, he met up with Oncology Times reporter Peter Goodwin to discuss the new data and their clinical potential.

Double checkpoint blockade using a single bispecific agent could become the new standard for treating advanced gastric cancer regardless of PD-L1 status, according to research reported at the AACR Annual Meeting 2024. The investigational bispecific antibody drug cadonilimab (used with chemotherapy) significantly extended life and delayed disease progression among patients with HER2-negative advanced or metastatic gastric or gastroesophageal junction cancers reported from Chinese investigators. The first author of the report, Jiafu Ji, MD, PhD, DrPH, FACS, FRCS, Fellow of the Chinese Academy of Medical Science, as well as Professor and Chief of the Gastrointestinal Cancer Center at Peking University Cancer Hospital and the Beijing Institute for Cancer Research in China, called into the Oncology Times office at AACR after his talk to discuss his team's findings with Peter Goodwin, an OncTimesTalk correspondent.

Join Scrip's China-based editors Brian Yang and Dexter Yan in this Chinese/English podcast as they look at data presented to AACR by Chinese pharma firms and recent acquisitions of China-based companies. UK-based writer Andrew McConaghie also joins to provide his perspectives, including on the proposed US BIOSECURE Act. https://scrip.citeline.com/SC150164/China-Biotech-Podcast-AACR-BIOSECURE-European-Perspectives

Beating Cancer Daily is the #1 ranked Cancer Survivor Podcast in 2024, helping listeners daily in 73 countries with over 250+ episodes. Today is super fun because Saranne invites you to her unique “Pajama Party” guest episode! Join Saranne and award-winning NBC correspondent, cancer survivor, and cancer advocate Kristen Dahlgren in their hotel room at the American Association of Cancer Research (AACR) Conference. And yes, they really are talking to you in their pajamas as they spontaneously share Saranne's podcast microphone (on Saranne's bed) to let you in behind the scenes in San Diego at this massive international cancer conference with 22,000 cancer researchers and cancer experts. (See their Beating Cancer Daily pajama podcast episode photo @ComedyCures.)Learn why Kristen, a medical reporter for NBC, The Today Show, and The Nightly News for more than two decades, traded in her journalism credentials live on the air, just weeks ago, for a role on the frontlines of cancer advocacy.Laugh with these two cancer survivors as they share why “This is the most hopeful time in cancer research.”Dive deeper into why Kristen and Saranne are collaborating with the top scientists to accelerate cancer vaccine discoveries. You will uncover why you should care and then hopefully join their research movement. You can even win your very own “Cancer Research Pajama Party”!This is more than an episode; it's an invitation to be part of history with indomitable souls who are turning the fight against cancer into a mission filled with joy, humor, science, and unwavering dedication to others.Upon launching her “Pink Eraser Project,” Kristen was introduced to stage IV survivor Saranne, who has been cancer-free for decades and serving as a global patient advocate. In 1999, Saranne launched The ComedyCures Foundation from her chemo chair with a "Chemo Comedy Party." Saranne has dedicated her life to helping others find strength, courage, empowerment, and laughter in their fight against cancer. As a healthcare thought leader, cancer researcher, speaker, patient advocate, and happiness expert, Saranne's work has garnered recognition and support from prestigious organizations like the NIH/NCI, the United Nations, the World Health Organization, AACR, ACS, Komen, numerous universities, hospitals, and cancer organizations. Saranne's transformative strategies, research findings, fun, practical tips, and comic insights can be found throughout the Beating Cancer Daily podcast, helping listeners to navigate their treatment and survivorship with humor and resilience.Are you wondering How You Can Support Beating Cancer Daily and ComedyCures?Supporting ComedyCures will help us continue our essential programs and research. Your generosity will significantly impact cancer patients, caregivers, doctors, nurses, and researchers worldwide.Choose your level of support:• Supporter: $60 (or $5 per month)• Friend: $180 (or $15 per month)• Champion: $600 (or $50 per month)• VIP: $5,000 annuallyDonate HereShare the Laughter with Beating Cancer Daily Podcast.Do you love the podcast, or do you have a suggestion? Go to ComedyCures.org and record a message or write a note to Saranne.

In this interview from the American Association for Cancer Research (AACR) 2024 Annual Meeting, Dr. Alankrita Taneja, third-year Hematology/Oncology Fellow at Roswell Park Cancer Institute and Oncology Data Fellows Forum Member, speaks with Dr. Sundar Jagannath, Professor of Medicine (Hematology and Medical Oncology) and Director of the Center of Excellence for Multiple Myeloma at the Mount Sinai Icahn School of Medicine and Tisch Cancer Institute. At the meeting, Dr. Jagannath presented results of the phase 1/2 LINKER-MM1 trial of linvoseltamab, a CD3-directed B-cell maturation antigen (BCMA) antibody under investigation for relapsed/refractory multiple myeloma. In this follow-up conversation, Dr. Jagannath shares further insights into the trial, including: • The study design, which includes triple-class–refractory patients • The unique dosing schedule of linvoseltamab, which reduces the frequency of administration to improve patient convenience • The response, survival, and measurable residual disease (MRD) negativity outcomes demonstrated in the trial, including among high-risk patients • Management of side effects, including cytokine release syndrome (CRS), neutropenia, anemia, and infections • The future role of linvoseltamab in the treatment landscape for relapsed/refractory multiple myeloma as it advances through investigation • And more!

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Pfizer is planning to bring an RSV shot to adults aged 18-59, while Boehringer Ingelheim is facing staff layoffs due to biosimilar challenges. Amylyx made a rare move by pulling an ALS drug from the market. On the regulatory front, the FDA has approved CAR-T therapies from J&J and Bristol Myers for earlier use in myeloma patients. Sage's depression drugs are facing hurdles, with the first medicine approved for postpartum depression not gaining traction and challenges in launching its second drug. Real-world evidence is becoming increasingly important in comparative effectiveness research, highlighting the need for a new approach to sales team development and coaching in biopharma companies. The industry is experiencing various challenges and advancements that are shaping the future of healthcare.A new study found that GLP-1 receptor agonists like Novo Nordisk's Ozempic do not increase the risk of thyroid cancer. Another study presented at AACR suggests that drugs approved through accelerated approval may not always lead to clinical benefit. Merck and Kelun's anti-Trop2 ADC shows promise in gastric cancer, while Torl Biotherapeutics secures funding for ADC therapies. Less than half of cancer drugs approved via accelerated approval showed clinical benefit in confirmatory trials. There are also job listings and other news updates related to the pharmaceutical industry.The resurgence of a shelved radioactive cancer therapy is making a comeback after being developed abroad for decades. The radiotherapy market is growing, with estimates suggesting it could be valued at $8.8 billion by 2028. Radiotherapy is commonly used in oncology to destroy cancer cells, but it carries risks of damaging surrounding tissue. Precision medicine innovations, such as stereotactic body radiation therapy, are being developed to target tumors more accurately. There is also increasing focus on psychiatric drugs in the pharma industry, as well as challenges and opportunities in the biosimilar market. The text includes information about a survey on what emerging biotechs want from CROs and CDMOs, recent developments in the pharmaceutical industry like job cuts at Novartis and partnerships in cancer drug development, a poll about running clinical trials in Ukraine during the ongoing war, and offers links to resources on patient support hubs, emerging biotechs, and the obesity drug revolution.

Conference season is in full swing, with the American Association for Cancer Research and American College of Cardiology concurrently holding their annual meetings in San Diego and Atlanta, respectively. From opposite coasts, biopharma companies are presenting their latest data in the cancer and cardiology spaces, both hits and misses alike. Oncology continues to be a hot area for investment, with several highly anticipated readouts coming down the pike. In addition to all the data coming out of AACR, conference organizers this year put together the meeting's first-ever industry event, bringing together investigators, investors and Big Pharma. Over at ACC, one exciting race to watch will be between Ionis and Arrowhead, both of whom presented positive data on their ApoC3-targeting drugs for diseases associated with elevated triglyceride levels. Meanwhile, as the BIOSECURE Act sits before Congress, biopharma companies detail the potential fallout to the growing geopolitical tensions between the U.S. and China.

M&A has been driving a recovery for biotech, with $62 billion in takeouts in the past six months restocking specialist investors' coffers for their next wave of investments. On the latest BioCentury This Week podcast, BioCentury's editors assess the state of the public markets heading into the second quarter, including the outsize role PIPEs have had in financing industry's comeback. They also discuss their takeaways from analyzing nearly 7,000 abstracts from the American Association for Cancer Research and the editors' insights on why degrader-antibody conjugates are emerging as the next contenders to build on the success of the antibody-drug conjugates paradigm. Editor in Chief Simone Fishburn also previews Grand Rounds, BioCentury's first R&D conference, which will focus on the biotech industry's interface with academia, bringing together decision-makers and the next innovators in Nashville Sept. 9-11. To learn more about BioCentury Grand Rounds and opportunities to present, see the conference website. This week's podcast is sponsored by Jeito Capital. 

In today's episode of Beating Cancer Daily, Saranne takes us on an exhilarating journey to the annual AACR convention, a gathering of the world's leading oncological researchers committed to eradicating cancer. As a Stage IV cancer conqueror with no visible disease, she highlights the cutting-edge advancements and personal triumphs reverberating through the halls of this inspiring event. Saranne's perspective as a survivor, researcher, and patient advocate shines a light on how vital patient input is in the search for the next big breakthrough. Dive in as she discusses how anyone touched by cancer can leverage the AACR resources to become more involved, from learning about the latest research to supporting clinical trials. Let's harness the shared hope and collective effort to beat cancer daily.Meet Saranne Rothberg, Cancer Survivor and Laughter AdvocateIn 1999, Saranne launched The ComedyCures Foundation from her chemo chair with a "Chemo Comedy Party." Now cancer-free, she's dedicated her life to helping others find strength, courage, and laughter in their fight against cancer. As a healthcare thought leader, speaker, patient advocate, and health and happiness expert, Saranne's work has garnered recognition and support from prestigious organizations like the NIH/NCI, the United Nations, the World Health Organization, and numerous universities and cancer societies. Saranne's transformative strategies, research findings, fun, practical tips, and comic insights can be found in the "Beating Cancer Daily" podcast and the BCD Membership Circle, where she helps listeners navigate their treatment and survivorship with humor and resilience.Are you wondering How You Can Support Beating Cancer Daily and ComedyCures.org?By supporting ComedyCures.org, you'll help us continue our essential programs and research. Your generosity will significantly impact cancer patients, caregivers, doctors, nurses, and researchers worldwide.Choose your level of support:• Supporter: $50 (or $5 per month)• Friend: $150 (or $15 per month)• Champion: $500 (or $50 per month)• VIP: $5,000 annuallyhttps://www.paypal.com/donate?hosted_button_id=GDPQCM8PHJTWe Share the Laughter with Beating Cancer Daily Podcast.Do you love the podcast?Please share it with a friend and spread the laughter!

Experiencing muscle discomfort from statins? Curious about natural ways to alleviate these symptoms and boost your heart health? In this episode, explore the role of geranylgeraniol (GG) and coenzyme Q10 (CoQ10) in supporting muscles affected by statins with repeat guest, Dr. Barrie Tan, the world's foremost expert on annatto, geranylgeraniol (GG), vitamin K in the form of MK-4 and vitamin E in the form of tocotrienols. Get ready to discover the benefits of these essential compounds that support cardiovascular health and muscle function, especially in individuals taking statins. A scientist first and foremost, Dr. Tan earned his Ph.D. in chemistry/biochemistry from the University of Otago, New Zealand, and spent several years as a professor at UMass. Dr. Tan has committed himself to the research and development of phytonutrients — natural compounds found in plants that reduce and slow chronic disorders. Dr. Tan is credited with discovering a form of vitamin E called tocotrienol from three major sources: palm, rice, and annatto — a natural dye and food coloring derived from the seeds of the achiote tree, known for its potential health benefits, including antioxidant and antimicrobial properties. Editor of two prestigious books on tocotrienol and founder of the International Tocotrienol Conference, Dr. Tan was dubbed the “Tocotrienol King” by Dr. Stephen Sinatra, a highly respected and sought-after cardiologist. Dr. Tan has held roles of Chief Scientific Officer and Scientific Board Member for multinational organizations. His career includes periods working in association with the US Armed Forces and a Prince of Thailand. He has successfully launched multiple businesses in the nutrition industry and owns an array of patents and intellectual property, keeping him at the forefront of scientific innovation. He is an internationally celebrated and sought-after speaker, having presented at multiple respected conferences in the field including; IFT, ADA, ASN, IHS, A4M, NPA, AACR, ICIM, IAOMT, and the Academy of Nutrition and Dietetics. Dr. Tan is currently the President of American River Nutrition, a natural health R&D company he started with his wife, Elizabeth, in 1998. Described as a scientific pioneer, his mission is simple: improve the everyday health of people's lives through the rigorous application of DeltaGold® – the first-ever tocopherol-free tocotrienol product extracted from annatto, and the most potent form of vitamin E in existence today. Be sure to check out Dr. Tan's formulations for Designs for Health (use code BEN15 to save 15%): For the full show notes, visit: https://bengreenfieldlife.com/ggpodcast Episode Sponsors: Organifi: Go to Organifi.com/Ben for 20% off your order. Ned: Get 15% off Ned products with code GREENFIELD by going to helloned.com/GREENFIELD. Ipothecary: Go to ipothecarystore.com/ben and use code BEN20 for 20% off. Clearlight Sauna: Go to HealwithHeat.com and use code BEN for a discount and free shipping. Limitless Life Nootropics: Visit limitlesslifenootropics.com/bengpeptides and use the code BEN at checkout for an exclusive discount.  See omnystudio.com/listener for privacy information.

Dr. Shannon Westin and her guests, Dr. Herbert Duvivier and Dr. Richard Schilsky, discuss the paper “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study” published in the JCO. TRANSCRIPT The guest on this podcast episode has no disclosures to declare.  Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in-depth into articles published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN Oncologist and Social Media Editor of the JCO. As always, it is my pleasure to serve and bring this information to you.  Today, we will be discussing, “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.” And this was published in the JCO on August 10th, 2023.  None of the authors have any conflicts of interest to disclose.  Joining me today are two of the authors, Dr. Herbert Duvivier, the principal investigator of this arm of the TAPUR trial. Welcome. Dr. Herbert Duvivier: Thank you.  Shannon Westin: And then, of course, many of you know Dr. Richard Schilsky, who is the former CMO and Executive Vice President of ASCO and a principal investigator on the TAPUR study.   Dr. Richard Schilsky: Thank you, Shannon.  Shannon Westin: So, let's get going. I think the first thing would be great is to level set and make sure everyone knows exactly what this TAPUR basket trial is, the Targeted Agent and Profiling Utilization Registry study. Can you guys give the audience a brief description of the objective of TAPUR and maybe how it came to fruition?  Dr. Richard Schilsky: Sure. This is Richard Schilsky. Maybe I can start with that. The TAPUR study is a prospective, phase II, multi-basket, multi-center genomic-matching trial. Its primary objective is to identify signals of drug activity for targeted agents that are already marketed. But in the TAPUR study they are being used outside of their FDA-approved indication. The study, as you may know, was conceived in 2014, launched in 2016, and is still enrolling patients across the country. Really, the genesis of the study came from the fact that it began at the time where genomic profiling of patients with advanced cancer was becoming more commonplace. Genomic alterations that could be targeted by already marketed drugs were being identified. However, patients and doctors were having difficulty accessing these drugs because they were not used on label and were unlikely to be covered by insurance. And moreover, even if they could access the drugs, there was no organized mechanism to collect outcome data and report on the results of the patient experience receiving that treatment.  So those factors led to the development of TAPUR, which attempts to solve both the drug access problem by having collaborating pharmaceutical companies donate their drugs to the trial so they're available to patients at no cost, but also implements a structured data collection mechanism so all of the relevant clinical outcomes with the patients can be collected and ultimately reported. And that's how TAPUR came about. Shannon Westin: Well, it was so necessary, and I think we do so much of our oncology treatments off-label, but as we get more and more expensive drugs when we move away from chemotherapies and more targeted immunotherapies, it's very hard to get those drugs off label. So this was such a relevant and necessary trial that had to happen, and it's a great example of leadership that you had the vision to put this together through ASCO.  I think the natural next question for me is having not put patients on the TAPUR study, how does a patient join this study? How do they get started? Walk us through that. Dr. Herbert Duvivier: At our institution, normally, all the physicians are aware of the TAPUR trial through internal conversations. When they have patients who have been treated with multiple lines of standard therapy, usually the next step for them is to get NGS testing. We have a research team that reviews all NGS testing for these patients and knows the open arms of the TAPUR trial. And if there happens to be a particular patient who may match with one, they will inform the physician. It is then up to the physician to speak to the patient about that option.  Shannon Westin: Do you have people come looking for the TAPUR trial or are these generally more established patients? Dr. Herbert Duvivier: From my perspective, I think it is usually established patients. Shannon Westin: I think what I love about this trial, and I have spoken about this trial in lectures around baskets, it's such a pragmatic design making it as straightforward as possible to really implement across different centers, whether academic or community, or wherever they are. I guess one of the questions always around these targeted therapies is the molecular selection. How do you make sure that people are being appropriately molecularly selected and how do you decide which testing to utilize?  Dr. Richard Schilsky: As you pointed out, Dr. Westin, the goal of the study from the beginning was to have a very pragmatic design, in a sense to have this study attempt to replicate the way oncologists were deploying precision medicine in their practice. The study has broad eligibility criteria, it has minimum necessary data collection, it uses conventional clinical evaluations, there are no additional clinical evaluations required that are not part of routine clinical care. And it just makes it easy to embed the study into the clinical workflow. The study is based largely at community sites, about 85% of the 268 participating sites are located in smaller communities. The study has a set of genomic matching rules that are listed in the protocol and baked into the IT platform for the study as a rules engine. For every treatment available in TAPUR, there is a set of genomic inclusion and exclusion criteria.  So in essence the way it works, the physician determines that NGS testing is appropriate for their patient and can use any NGS test they want, as long as the test is performed in a CLIA certified, CAP, or New York State-accredited laboratory. They select the test, they select the biospecimen to be tested, they get the results, they look at the results, and they determine if there is a genomic alteration in the patient's tumor that is targeted by one of the study treatments in the TAPUR study. They can enter that into the rules engine, the rules engine will confirm or not that the appropriate alteration of treatment has been selected. If it is confirmed, then the patient can immediately be enrolled in the study if they meet the clinical inclusion and exclusion criteria.  If the rules engine does not confirm the treatment match is appropriate, or in some cases there are multiple possible treatment matches, if there are multiple alterations that can be targeted, or another case is the doctor is simply uncertain about which alteration is best to target, then the clinical site can send that patient case to the TAPUR molecular tumor board. A group of experts convenes weekly that reviews the clinical history, the pathology report, genomic test report, the prior therapy the patient has received, and they make a determination as to whether or not there is an appropriate therapy that's available on TAPUR for the patient. And if not, then are there other potential therapies  that are available that could be considered. That information is sent back to the treating physician who determines whether or not here she feels that treatment option is appropriate for their patient, and if so, the patient can then be enrolled and receive the therapy. Shannon Westin: So awesome. I love the idea. If we don't have an arm for you on our trial, we can help assist you potentially determine an option for your patient outside of that. That's so clever.  Okay. So let's get into this particular arm. Obviously, our audience is quite savvy and are aware of the role of immune checkpoint inhibition across a number of solid tumors. Could you describe what you sought to determine in this particular arm of the TAPUR study?  Dr. Herbert Duvivier: I think one of the most important things to remember about this study is that this study was opened and accruing prior to pembrolizumab becoming FDA approved in, I think, June of 2020. So prior to June of 2020, there was no indication for pembrolizumab in high TMB tumor types and the goal of the study was to determine if pembrolizumab had any overall response rate, duration of responses, progression-free survival, or overall survival advantage over what would be considered standard chemotherapy at that time in patients with high TMB. Dr. Richard Schilsky: Yeah, that's exactly right. And in this paper that we're discussing, we're reporting on two different groups of patients. So there's a group of 28 patients, all with colorectal cancer, all of whom had high tumor mutation burden, as defined by the protocol. And that's one group. Then there's a second, larger group of patients, which is a very heterogeneous group of solid tumor patients. And the reason that that group is reported is there were patients who were being enrolled with multiple different tumor types with high tumor mutation burden. Each tumor type determined a specific, tumor-specific cohort in the study, and they were enrolling at different rates depending upon how common the particular tumor type was. But once the FDA approval for pembrolizumab, for any tumor with a high tumor mutation burden, was granted, then all of those cohorts essentially had to close to new enrollments because there was no longer an off-label use for pembrolizumab in that setting - everything was now on the label.  The result was that we then basically collapsed all of the open cohorts that were not then going to be able to complete into this one large, heterogeneous cohort that's being reported in this paper. And going back to the colorectal results, in the paper, we describe a disease control rate of 31%, an objective response rate of 11%. There were three patients who had partial responses lasting 12, 27, and 97 weeks each. And I think it's important to point out that in this particular cohort, essentially all of the colon cancer patients were microsatellite stable. So that's an interesting nuance here because we know that pembrolizumab is active and has an FDA approval in microsatellite high tumors. But this particular group of patients was essentially all microsatellite stable, suggesting that even in that population, if the tumor also has a high tumor mutation burden, the patient has the potential to respond and benefit from the treatment. Shannon Westin: I found that very intriguing. And, of course, as a gynecologic oncologist that treats endometrial cancer, I'm always thinking about MSI and microsatellite stability. So I was very intrigued by this. We are not seeing a ton of TMB high in our population, but there are some patients that do have that.  So let's talk a little bit about the results for the collapsed all solid tumor group. What did you find there? Dr. Herbert Duvivier: In the histology pool cohort, there were 47 patients representing 21 different tumor types, with a median tumor mutational burden of approximately 13 mutations per megabase with a range of 9 to 228. 40 of 47 patients had MSS disease, microsatellite stable disease. 6 of the 47, MSS was not reported, and 1 case was ambiguous. The disease control rate was about 45%, and the objective response rate was 26%. There were 3 complete responses: 1 in bladder, 1 in parotid, and 1 in squamous cell carcinoma. 9 partial responses and 9 stable disease 16 plus weeks. Of interest in the patients that were responding, 10 out of the 21 patients had POLE or POLD1 mutations, and 9 of the 21 patients had BRCA1 or BRCA2 mutations, although most of those mutations were classified as variants of uncertain significance. Shannon Westin: That's really interesting. We've seen pretty good data for POLE and benefit from immunotherapy, although at least in the GYN tumors and especially in endometrial cancer, those patients usually do well no matter what you do with them. And so they don't often make it to get immunotherapy because they have a complete response up front to their surgeries. So very intriguing to see that driving benefit. I'm just interested to see because it seems like there's a range that you were quoting of what was considered to be TMB high. So did you see a correlation for response to therapy based on how high the tumor mutational burden was in a given tumor or tumor type? Dr. Herbert Duvivier: Yes, actually we did see a moderately negative correlation between maximum percent change from baseline in a tumor and increasing TMB, which indicated an association between a higher TMB and greater shrinkage of tumor lesions. Dr. Richard Schilsky: I should point out, by the way, that when we introduced this arm into the TAPUR study, this high tumor mutation burden arm, as Dr. Duvivier has already pointed out, it was prior to, of course, the FDA approval, and the FDA approval is for tumors that have at least 10 mutations per megabase. It was also prior to the adoption of that threshold of 10, based on work by Friends of Cancer Research and others as sort of the convention for what defined a high tumor mutation burden. So when we put this into TAPUR, we essentially consulted with some of the testing laboratories. We consulted with Merck, the sponsor for pembrolizumab and actually in the TAPUR study, we defined a threshold of 9 mutations per megabase as defining high tumor mutation burden.  Now, as Dr. Duvivier said, there's a broad range of tumor mutation burden represented in this population, and there does seem, if you look at, if the readers want to look at figure 4 in our paper, there does seem to be a general correlation between best response and number of mutations per megabase, which also holds true in a modest way for both progression-free and overall survival. So, TMB is somewhat predictive of favorable outcomes. It's not a perfect biomarker by any means, but generally speaking, if you have enough patients, you can define this sort of trend to support the notion that the more mutations, the greater the likelihood of benefit. Shannon Westin: That makes a lot of sense. One other thing that I just wanted to comment on before we kind of bring the podcast to a close is I was really struck by the high proportion of underrepresented minorities in this arm of TAPUR, and I just would love to hear your thoughts on how the design improves recruiting in this population of patients. Dr. Richard Schilsky: This was a goal of the study, very intentional. When you look at the overall study demographics, there are about 2800 patients now that have been enrolled on TAPUR overall. Almost 12% are black, about 6% are Hispanic, about 4% Asian. The median age is about 64. So it's a slightly older population. The goal always was to enroll a population of patients in TAPUR that was broadly representative of the patients that oncologists treat in practice. In the way we accomplished what we've accomplished, we still have work we can do to improve it. But the clinical sites were carefully selected and vetted. We focused on sites that served a significant fraction of minority patients. We made the eligibility criteria simple and broad, so many of the eligibility criteria that might typically exclude minority populations or older patients from clinical trials are not exclusion criteria in TAPUR. We made the operations of the trial simple, so patients really aren't asked to do much more than what they would normally be asked to do in the course of their routine cancer care. So I think all of those things together have made it possible to attract and enroll a more representative patient population in the study. And we're very gratified by that because when you look at many of the registration trials for many cancer drugs, minorities and older people are terribly underrepresented. So we feel that TAPUR is adding value there and adding useful information. Shannon Westin: I think it's so generalizable and really the way people are practicing, and so to see similar results or concordant results, despite not as much of the rigorous testing and potentially exclusion of certain patient populations is really reassuring and certainly very exciting.  The last question is what's coming next? What other arms are coming soon? And can sites still join? Is this something where it's ongoing enrollment and participation? Dr. Richard Schilsky: So sites can still join. There's a place on the ASCO website where sites can find more information about TAPUR, and there's essentially a form available where sites can indicate their interest in joining the study. And then those sites are then evaluated by the TAPUR study team to determine if they meet the minimum necessary requirements to qualify to join the study. There's a lot more data coming out, many more papers that are in press and being written. There are two abstracts that will be presented in April at the AACR meeting. There are three abstracts that have been submitted for the ASCO annual meeting. So a lot more data to come.  This is a study that, at least hypothetically, could continue in perpetuity as long as we're able to continue to attract new drugs and new treatment combinations onto the TAPUR study platform. So the TAPUR team is always on the lookout for drugs that are about to get an FDA approval and that could be appropriate for the TAPUR study and continue to talk to many pharmaceutical companies about their interest in potentially putting their drugs on the platform. Shannon Westin: Well, great. Thank you both for taking the time. I know you're both incredibly busy.  Again, this has been “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.” I'm your host, Shannon Westin, and I'm so grateful that you joined us on JCO After Hours. Please check out our other offerings on the website or wherever you get your podcasts. Have an awesome day.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Duvivier's COIs: Speakers' Bureau Company name: Guardant Health Company name: AstraZeneca Company name: Regeneron  Schilsky's COIs: Leadership Company name: Clarified Precision Medicine Company name: Leap Therapeutics Stock and Other Ownership Interests Company name: EQRx Company name: Leap Therapeutics Consulting or Advisory Role Company name: Cellworks Company name: Scandion Oncology Company name: Bryologyx Company name: Illumina Company name: EQRx Company name: Syapse Company name: Zephyr AI Company name: AADi Research Funding Company name: AstraZeneca Company name: Bayer Company name: Bristol-Myers Squibb Company name: Genentech/Roche Company name: Lilly Company name: Merck  

BUFFALO, NY- March 11, 2024 – Impact Journals publishes #scholarly journals in the #biomedical sciences with a focus on all areas of cancer and aging research. Oncotarget is one of the most prominent journals published by Impact Journals. Impact Journals will be participating as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2024 from April 5-10 at the San Diego Convention Center in San Diego, California. This year, the AACR meeting theme is “Inspiring Science • Fueling Progress • Revolutionizing Care.” Visit booth number 4159 at the AACR Annual Meeting 2024 to connect with members of the Oncotarget team. About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us on social media at: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

BUFFALO, NY- March 11, 2024 – Impact Journals #publishes scholarly #journals in the #biomedical sciences with a focus on all areas of cancer and aging research. Aging is one of the most prominent journals published by Impact Journals. Impact Journals will be participating as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2024 from April 5-10 at the San Diego Convention Center in San Diego, California. This year, the AACR meeting theme is “Inspiring Science • Fueling Progress • Revolutionizing Care.” Visit booth number 4159 at the AACR Annual Meeting 2024 to connect with members of the Aging team. Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer's diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases. Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

In the classic holiday film "It's a Wonderful Life", Clarence the angel says "remember, George, no man is a failure who has friends". In the holiday spirit, Your Doctor Friends took Clarence's words to heart, and present to you today the research behind how friendship keeps us healthy. In today's episode, we highlight the growing amount of evidence that supports friendships as a key aspect of our health, and, conversely, how social and emotional isolation often leads to poor health outcomes. The American Psychological Association summarizes, “given the clear benefits of friendship, psychologists say we should promote platonic social connection across society—including in school, at work, in public spaces (such as on public transportation), and through entertainment.” So let's do that today, shall we? And after listening to the episode, maybe reach out to a friend with a quick text, a silly photo, or an invite to meet up for a treat together. It might just help you live longer ;) And bonus dessert topic at the end, we talk about SOME GOOD NEWS in cancer treatment and survivorship! Happy holidays from Your Doctor Friends! We hope you're safe, happy, and healthy :) Resources for today's episode include: An American Psychological Association article titled "The science of why friendships keep us healthy". A Washington Post article titled "Friends can improve your health and well-being especially during the holidays". A systematic review/meta-analysis in PLoS One from 2023 titled "Social isolation as a risk factor for all-cause mortality" A Healio article titled "Cancer death rate drops by 33%, AACR report shows" The AACR press release for the Cancer Progress Report. The full AACR Cancer Progress Report 2023. For more episodes, limited edition merch, or to become a Friend of Your Doctor Friends (and more), follow this link! This includes the famous "Advice from the last generation of doctors that inhaled lead" shirt :) Also, CHECK OUT AMAZING HEALTH PODCASTS on The Health Podcast Network   Find us at: Website: yourdoctorfriendspodcast.com  Email: yourdoctorfriendspodcast@gmail.com  Connect with us: @your_doctor_friends (IG) Send/DM us a voice memo/question and we might play it on the show! @yourdoctorfriendspodcast1013 (YouTube) @JeremyAllandMD (IG, FB, Twitter) @JuliaBrueneMD (IG) @HealthPodNet (IG)

Drs. Diwakar Davar and Ben Boursi discuss the role of the gut microbiome in the outcome of cancer immunotherapy and the prevention of immunotherapy-related adverse events, as well as compelling research on nutritional interventions to improve response to immune checkpoint inhibitors. TRANSCRIPT   Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center.   Researchers have shown that microorganisms in the gut can impact the effectiveness of immunogenic chemotherapy for patients with cancer. Although microbial therapies for cancer are still at a very early stage of clinical development, compelling research in recent years has shown that changing the gut microbiome can help improve outcomes in patients receiving treatments for cancer enduring immune checkpoint inhibition.  My guest today is Dr. Ben Boursi, a GI medical oncologist at the Sheba Medical Center at Tel Aviv University in Israel. Dr. Boursi is also an adjunct professor at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania. He joins me today to discuss his pivotal research on the role of the gut microbiome in mediating its effects on immunotherapy. And again, I want to highlight that we're recording this on October 9th, and as you may well know, many recent events over the last couple of days have happened in Israel, and so Dr. Boursi has joined us at a very difficult time. So, we're very grateful for him taking time out of his suddenly very busy schedule to join us at a time that is fraught for all. You'll find our disclosures in the transcript of this episode. You'll also find the disclosures of all guests on the podcast at asco.org/DNpod. Ben, it's great to have you on the podcast today. Thank you for being here at such a difficult time, sharing what will, I think, be a great episode.  Dr. Ben Boursi: Thanks for having me, Diwakar. Dr. Diwakar Davar: Ben, the gut microbiome and its role in terms of mediating effects and side effects of cancer immunotherapy has gotten a lot of interest recently. You've done some fundamental work in this space. Why don't you briefly summarize for the audience, firstly, what is the gut microbiome and what are the major themes in relation to cancer immunotherapy?  Dr. Ben Boursi: Well, the microbiome is the ecosystem of microorganisms, bacteria, phages, fungi, that are crucial for immunologic, metabolic and hormonal homeostasis of the host. In the last decade, we began to understand the central role of the gut and tumor microbiome in tumorigenesis, metastasis, treatment efficacy and toxicities, and in 2022, polymorphic microbiomes became one of the hallmarks of cancer, in addition to previous hallmarks that focused mainly at the cellular/genetic levels. The initial studies in mice models showed that therapeutic efficacy of immunotherapy depends on both the presence and composition of the microbiota (In germ-free or antibiotic treated mice, immunotherapy is ineffective), and following these studies, three observational studies in human patients showed that the gut microbiome can predict response to immunotherapy and that response to immunotherapy could be transferred to germ-free mice by fecal microbiota transplantation (FMT) from responding patients.  These studies helped us to define three main research questions regarding the possible role of microbial modulation in cancer treatment. First, can microbial modulation overcome resistance to immunotherapy, both primary and secondary resistance? And this question was the focus of the initial proof of concept studies. Second, can microbial modulation improve response to immunotherapy in treatment-naive patients? And third, can microbial modulation prevent or treat immune related adverse events? The initial positive results of clinical trials also led to additional questions. For example, can microbial modulation induce anti-tumor immune response even in non-immunogenic tumors? And it is important to note that there are many ways to modulate the microbiota, but so far, the only reliable way that showed positive results is fecal microbiota transplantation that allows the transfer of the entire microbiota both in terms of composition and relative abundance. Dr. Diwakar Davar: That's great. Essentially with the trials that I think the data sets that you're referencing of course, are papers by Jennifer Wargo, Thomas Gajewski, and Lawrence Zitvogel, looking at the role of gut microbiota in several different cancers, primarily immune checkpoint sensitive tumors such as melanoma, non-small cell lung cancer and kidney cancer. And then the work from several different groups showing that essentially proof of concept experiments can be done to try to change this, certainly preclinically, and now we know that that can be done clinically.   So, I guess the failure rates of immunotherapy in some patients are quite high. And we know that the microbial composition can change the likelihood to respond to immunotherapy based on all these trials. And actually, even going back to 2015, we had two seminal papers that looked at the role of CTLA-4 blockade as well. But subsequently, many years after that, 7 years after 2015, and certainly 3 years after 2018, when the three observational PD-1 papers were published, there were 2 pivotal trials in PD-1 advanced or refractory melanoma. They demonstrated that changing the gut microbiome can reprogram the immune system to attack tumors. So, there were 2 separate trials, both published the same issue of Science. One trial was led by your group at Sheba, and another one's led by us, the University of Pittsburgh. Why don't you summarize both studies for our audience. Dr. Ben Boursi: So, both studies were Phase I clinical trials of FMT in metastatic melanoma patients who failed immunotherapy. Recipients were metastatic melanoma patients that progressed on at least one line of anti PD-1 and in BRAF mutated patients, BRAF inhibitors as well. Donors in the Sheba study were metastatic melanoma patients with durable complete responses to immunotherapy for at least one year, and in the Pittsburgh study, you also included patients with durable partial responses of more than two years as donors. It is important to note that each fecal transplant in both studies was composed of a single donor. Prior to transplantation, we performed a microbiome depletion phase using a combination of two antibiotics, vancomycin and neomycin. The goal of this phase was to assist in engraftment (by avoiding colonization-resistance by recipient bacteria) and to “reset” the immune system, which may remind some people of the logic behind bone marrow transplantation. In the Pittsburgh study, there was no bacterial eradication with antibiotics, mainly because of studies showing that response to immunotherapy is lower following antibiotic treatment.  Both studies performed FMT through colonoscopy. At Sheba, we also performed maintenance FMT using capsules in order to keep the donor's microbial composition. After the initial FMT, both studies reintroduced the same immunotherapy in which the patient progressed in the past. Clinically, we have seen a 30% response rate with durable, complete and partial responses, and in the Pittsburgh study, there was a 20% response rate and 40% disease control rate. Both studies showed following FMT, immune response in the gut and in the tumor, and tumors that were immune deserts prior to FMT became infiltrated with lymphocytes. Interestingly, in our study, there were no moderate to severe immune related adverse events following FMT and reintroduction of immunotherapy. And this is despite the fact that five of the patients had significant side effects during previous rounds of the same immunotherapy.  Dr. Diwakar Davar: So essentially, in these very early proof of concept studies, what I think is pretty remarkable is that obviously the sample sizes were very small, but remarkably, patients that appeared to respond, responded in a setting in which they were not expected to respond. So, the probability of a patient responding to attempt at giving PD-1 in patients who were PD-1 relapse refractory is on the order of about 7%, based on an FDA analysis by Viva et al. And here, two separate studies, two independent studies, investigators had not known that each paper was being published, remarkably similar results clearly demonstrating that this is perhaps one of the best pieces of evidence to suggest that microbiome modulation may actually truly be effective in reversing PD-1 refractoriness.  More recently, our colleague Dr. Bertrand Routy at University of Montreal has done a proof of concept trial in evaluating the use of healthy donor fecal microbiota transplant in addition to anti PD-1 monotherapy in PD-1 naive metastatic melanoma. In this study, published in Nature Medicine a few weeks ago, his group reported an objective response rate of 65%. What are your thoughts about this study? And specifically, what are your thoughts about some of the pharmacodynamic and translational results that were demonstrated?  Dr. Ben Boursi: This is a very interesting question, because in both the Sheba and the University of Pittsburgh studies we chose responding patients as donors. We thought that by using these patients, we provide beneficial bacteria that enhance responses to immunotherapy through several mechanisms (molecular mimicry, immunomodulatory bacterial metabolites, modulation of immune checkpoint expression, and much more), and here in the Routy paper, the researchers used FMT from healthy donors without any selection for specific beneficial bacteria, and they demonstrated a similar effect on overall response rate. So maybe FMT works actually through reducing colonization by deleterious bacteria? Another question that we should ask is whether we need to choose donors differently when we use microbial modulation in treatment resistant patients compared to treatment-naive patients? Moreover, a previous meta-analysis of FMT studies across indications that was conducted by the group of Dr. Nicola Segata, demonstrated that recipients with better engraftment were more likely to experience clinical benefit, and that increased engraftment was mainly observed in individuals receiving FMTs through multiple routes, colonoscopy and capsules, as well as recipients that received antibiotics prior to FMT. But in Routy's trial, they not only used healthy donors, they performed bacterial cleansing only prior to FMT instead of bacterial eradication with antibiotics, and used FMTs through colonoscopy only, and they didn't give maintenance FMT. Of course, such an approach is much more feasible in the clinical setting and is relevant for designing future clinical trials.  Dr. Diwakar Davar: So, many differences, relatively few similarities, but I guess one interesting point is that of engraftment, which is that in your paper, our paper, and certainly in Bertrand's paper, it is very interesting that engraftment appears to be a key pharmacodynamic biomarker of microbiome modulation. And certainly, the analogy that you used earlier, which is that it's very similar to what happens in a stem cell transplant, which is that if there's no take, there's probably not going to be any effect. So that's very interesting that engraftment is emerging as a key PD biomarker of essentially the success of any kind of microbiome modulation across multiple different settings.  Now, we've heard of certainly defined microbial consortia, of cultivated species, as an alternative gut microbiome modulation strategy that balances the benefits of the ecological complexity of FMT with the scalability and practicality of probiotics. Do you think we are ready to design consortia?  Dr. Ben Boursi: So to date there are several probiotics that use a single bacteria and several microbial consortia that were evaluated in clinical trials, and as you mentioned, they may offer more tractable solutions for widespread clinical use. If we begin with the single bacteria probiotics, two phase 2 clinical trials found that administration of the butyrate producing probiotic clostridium butyricum 588 (CBM588) to immunotherapy naive patients with metastatic renal cell carcinoma led to markedly better immunotherapy responses, although the probiotic had a minimal effect on the composition of the microbiota, and the control arm of the trial responded worse than expected. In addition, in preclinical studies, probiotic strains of lactobacillus and bifidobacterium have been shown to enhance immune control of transplanted tumors and to augment anti PD-1 activity. However, a clinical trial in patients with metastatic melanoma found that the use of lactobacillus or bifidobacterium probiotics was associated with reduced microbiota diversity and worse responses to anti PD-1.  So here the conclusion is that when we try to design probiotics, we should not focus only on the composition since other factors, such as the relative abundance also matter. Too much of a beneficial bacterial species may potentially be worse than having a balanced and diverse microbiota. For example, a recent study of patients with non-small cell lung cancer receiving immunotherapy found that patients with a detectable Akkermansia muciniphila in their gut microbiota (this is a beneficial bacteria) responded well to treatment, but those with relative abundance of Akkermansia muciniphila greater than 5% responded worse than patients lacking Akkermansia, and this is due to the mucolytic effect of the bacteria. So, the use of rationally designed consortia may be better than a single probiotic strain.  And there are currently 3 main microbial consortia that are being evaluated: the SER-401, a bacterial consortium enriched with clostridium, led in a randomized controlled trial to reduced response to immunotherapy compared to placebo control in first line metastatic melanoma patients, potentially due to a confounding effect of a vancomycin pretreatment; MET4 is a 30 bacteria consortium that was shown to be safe and to alter the gut microbiota and serum metabolome of immunotherapy naive patients. Here, the initial study was underpowered to determine the effect on treatment efficacy; And finally, VE800 is an immunotherapy enhancing 11-bacterial consortium that is currently being evaluated in phase 1 and 2 clinical trials, and we are looking forward to see the results with this agent. Dr. Diwakar Davar: So I guess where we are right now is that social design is clearly difficult because of all the reasons you've mentioned. The SER-401 data and the MET4-IO trials certainly give us pause for thought. Certainly, no pharmacodynamic changes that were seen with SER-401, MET4-IO did result in pharmacodynamic shifts metagenomically, but neither trial was positive. And certainly, the VE800 trial, which has been ongoing now for several years, and the lack of publicly reported data certainly doesn't suggest that there's a huge efficacy signal. So consortias, at least at this point, certainly do not appear to be having a significant effect, though we don't know what might happen in the future. Data from multiple groups has shown that gut microbial composition influences the development of immune related adverse events (irAEs) in both PD-1 and combination PD-1 and CTLA-4 treated patients. Unsurprisingly, as a result, there have been attempts made at evaluating the role of fecal microbiota transplants to treat refractory immune related adverse events and very specifically immune checkpoint associated colitis or IMC. So, Dr. Yinghong Wang, who is the chair of the Immunotherapy Toxicity Working Group at the University of Texas MD Anderson Cancer Center has been very prominent in this space, and in a recent paper published in Science Translational Medicine, which is a follow up paper to her early work in Nature Medicine, she reported that HDFMT, healthy donor fecal transplantation, was very efficacious in feeding early refractory immune checkpoint colitis. So, what are your thoughts on this approach and how important is this space and where else might it be efficacious?  Dr. Ben Boursi: When I talked about the Sheba clinical study, I mentioned the possible role for microbiota modulation in the prevention of immunotherapy related adverse events in general, not only colitis. But the study by Dr. Yinghong showed that FMT can actually treat immune-related colitis refractory to steroids and anti-TNF. Now, this approach is probably relevant not only for immune related colitis, but also to other immune related adverse events. We can define certain bacterial species that may be associated with different immune related events. For example, streptococci can be associated with immune related arthritis. And maybe in the future we won't need to use FMT, but we will rather be able to target these specific immunogenic strains by narrow spectrum antibiotics or phages. The main challenge would be to develop microbiotic targeting interventions that reduce immune related adverse events without compromising therapeutic efficacy.   Now, is microbial modulation relevant only for toxicity from immune checkpoint inhibitors? So, the answer is ‘no'. We know mainly from animal models of hematopoietic cell transplantation, CAR T, and immune agonist antibodies that antibiotic-treated or germ-free mice have markedly reduced immunotoxicity, such as graft versus host disease, cytokine release syndromes, and more. It is also worth mentioning that microbial modulation is relevant not only for reducing toxicity from immunotherapy, but also from chemotherapy and other anticancer modalities. And the best example is the gastrointestinal toxicity of irinotecan that is mediated by the bacterial beta-glucuronidase. And here the targeting may even be a bit less complex. Dr. Diwakar Davar: So, what we take away from that is that starting with actually your paper originally, and papers to be produced, immune-related adverse events can be prevented using microbiome modulation with FMT, and Dr. Wang's data suggesting that eventually FMT can be used to eradicate highly refractive colitis, again, this is important to keep in mind that this approach is not yet FDA-approved. It's being done under IND. It's not currently something that is a certain standard of care. One interesting area of drug development is that there's a French microbiome company named MaaT Pharma where they have an agent that is a very interestingly a pooled microbiome product from multiple different donors. Again, the trials in both Israel and Pittsburgh used individual donors. This is a pooled donor construct. The lead candidate is actually graft versus host disease. The trial is the ARES trial, A-R-E-S, as in the Roman god of war. This trial is actually ongoing in Europe, and I believe there's some effort to try to see whether or not it's going to be a trial that can be done in the United States as well. So, at this point in time, again, we don't know whether or not there are any developmental approaches from a pharmaceutical company in the United States, but certainly this is definitely an area of interest.  So microbial therapies are still relatively early. It's going to be interesting to see how the advanced field of nutritional interventions provide an appealing method for modulating the gut microbiome due to the excellent safety profile, cost effectiveness and noninvasiveness. And certainly, if you are what you eat and your bacteria are what they eat, which goes down to our diet, there's enough rationale to believe that certain nutritional interventions can have an effect via the intermedial gut microbiota modulation. Holistic dietary changes and or supplementation specific nutrients such as prebiotics could therefore be utilized to specifically shape the population of beneficial microbes and shift the immune microbiota landscape. Now, we have seen in data published by several of our colleagues that in patients with cancer, high fiber intake is associated with greater microbial diversity, greater abundance in fiber fermenting microbes such as members of the Ruminococcaceae family, and these are all associated with the response to checkpoint inhibitor therapy. So, what do you think about nutritional interventions? Do you want us to briefly summarize data regarding nutritional data and where it stands in cancer at his time? And can you speculate as to how effective this might be in the context of patients with cancer? Dr. Ben Boursi: So, let's begin with diet. A growing number of clinical and preclinical studies suggest that specific dietary interventions such as a high fiber diet can not only improve response to immune checkpoint blockers, but also reduce immunotoxicity such as graft versus host disease. And there are many other diets that are being tested such as ketogenic diets and intermittent fasting. And the effects of diet may be mediated by both microbiota-dependent and microbiota-independent mechanisms. The limitation of this approach is that changes to the microbiota induced by diet are generally quite variable between patients and can depend on an individual's microbiota prior to intervention. And patient compliance is also a concern, particularly in the very strict diets.  Now, regarding high fiber diets, several large cohorts of melanoma patients from the US, Australia, and the Netherlands demonstrated how a high fiber diet modulates the microbiome and results in a better response to immunotherapy, better progression-free survival. Additional studies that were presented at AACR in 2023 showed that high fiber dietary interventions, in which patients received a fiber-enriched diet for six weeks, was feasible and that the high fiber diet resulted in a rapid shift in the gut microbiota toward fiber-responsive short chain fatty acid-producing taxa and a shift of the metabolome, with increase in the short chain fatty acid acetate, Omega-3, Omega-6, polyunsaturated fatty acid, and tryptophan metabolites. Prebiotics can also promote the growth of beneficial microbial species in the gut by providing targeted nutrition. And one example of a prebiotic that was shown to enhance immunotherapy efficacy in mouse models is castalagin, which is isolated from the camu-camu berry. Castalagin directly binds the outer membrane of ruminococci and promotes their growth, which has been shown to increase the CD8-positive T-cell activity and anti-PD-1 efficacy. Now, since prebiotics rely on the presence of beneficial taxa already in the host microbiota, symbiotics, which refers to the administration of the appropriate prebiotic and probiotic together, may prove in the future to be more effective than using either separately. Dr. Diwakar Davar: Certainly, these dietary interventions can be very exciting and certainly we do know of several colleagues who are doing these diet interventions, though compliance with any kind of dietary intervention may be a challenge that decides how effective such an approach is going to be. So microbial therapies in general are still at a relatively early stage of development. And it'll be exciting to see how they advance. What approaches are you excited about? What is on your radar?  Dr. Ben Boursi: There are many exciting works that are currently ongoing, and to emphasize just a few: there are many clinical trials in immunogenic tumors, in addition to melanoma, for example, renal cell carcinoma, and non-small cell lung cancer, that also evaluate different modulation protocols. We should remember that one size does not fit all, and different tumors have different microbiomes. We have a project in collaboration with MD Anderson in MSI-high patients with exciting initial results. Another study that was initiated at Sheba is using microbial modulation in order to improve TIL therapy (to overcome resistance to TIL and T-cell exhaustion). There are also studies that try to change the pharmaco-microbiome, for example, to eradicate bacteria that inactivates the chemotherapy agent, gemcitabine, in pancreatic cancer patients. And there are groups that try to identify recipients that will respond to microbial modulation and to generate better donor-recipient matching algorithms. There are already signatures like TOPOSCORE that was presented at ASCO 2023 that try to predict response to immunotherapies through the ratio between harmful and beneficial bacteria. Now, there's also more basic science work, for example, bacterial engineering. There was a wonderful study from the Fischbach group in Stanford that demonstrated how Staphylococcus epidermidis engineered to express melanoma tumor antigens was able to generate a systemic tumor-specific response in mice models when applied topically; functional imaging of the microbiome, for example, FDG uptake in the colon can reflect microbial diversity and response to immunotherapy; works that characterizes other microbiomes such as the urinary and skin microbiomes, and their interaction with the gut microbiome; and studies of the nonbacterial component of the microbiome, mainly phages and fungi. But for me, the most important word should probably be collaboration, because without joining forces internationally, we won't be able to understand the human metaorganism, the variations according to geography, ethnicity, lifestyle, diets, and much more in the microbiome. And this is crucial in order to really understand the complex tumor ecological niche within the human host. Dr. Diwakar Davar: I think one of the key points that you just mentioned is collaboration. That's going to be very, very critical as we move this forward for many reasons, including the unexpected impact of geography upon the composition of the gut microbiome in work that has been published by many groups, but also including ours in a paper that we published about a year ago now.  So, Dr. Boursi, thank you for your great work in this area. Thank you for sharing your insights with us today on the ASCO Daily News Podcast. This is a very difficult time for all of you and your colleagues in Israel, and we thank you so much for taking such a great deal of time out of your busy workday to spend some time with us.  Dr. Ben Boursi: Thank you very much. Dr. Diwakar Davar: Thank you to all our listeners today. This is a very exciting area. This is an area where we are discovering more every day than we knew just up until the day prior. You will find the links to the studies that were discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take the time to rate, review, and subscribe wherever you get your podcast.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Diwakar Davar  Dr. Ben Boursi   Follow ASCO on social media:   @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Ben Boursi: No relationships to disclose.        

Drs. Hope Rugo and Nancy Davidson discuss the next generation of endocrine therapy in hormone receptor-positive breast cancer – SERDs, SERMs, CERANs, and PROTACs – and challenges relating to the optimal sequence of therapeutic options. TRANSCRIPT Dr. Hope Rugo: Hello, I'm Dr. Hope Rugo, your guest host of the ASCO Daily News Podcast today. I'm a professor of medicine and director of breast oncology and clinical trials education at the University of California San Francisco's Comprehensive Cancer Center. Hormone receptor-positive (HR+) breast cancer is the most common subset of this disease and breast cancer is the most common cancer diagnosed in women worldwide. Endocrine therapy (ET) is the cornerstone of management in hormone receptor-positive breast cancer and may involve suppressing estrogen production with aromatase inhibitors in the cancer cell itself, or directly blocking the estrogen receptor pathway through selective estrogen receptor modulators, such as tamoxifen, or the injectable selective estrogen receptor degrader, fulvestrant. However, despite the availability of these therapies, the largest unmet need lies in treatment of HR-positive HER-negative disease lies after progression on endocrine therapy. On today's episode, we'll be discussing the emerging generation of endocrine therapies in breast cancer, some of which were designed to overcome common mechanisms of endocrine resistance, and the challenges relating to the optimal sequence of therapeutic options. Today, I'm delighted to welcome the world-renowned breast cancer researcher, Dr. Nancy Davidson, to the podcast. She's a professor and the executive vice president for clinical affairs at the Fred Hutchinson Cancer Center and professor of medicine at the University of Washington as well as past president of ASCO and AACR. You'll find our full disclosures in the transcript of this episode and disclosures of all guests on the podcast can be found in our transcripts at asco.org/DNpod. Nancy, it's great to have you on the podcast today. Thanks so much for being here. Dr. Nancy Davidson: Thank you so much, Hope, for the opportunity. Dr. Hope Rugo:  You've done incredible work in the area of treating HR+ disease, but also in understanding some of the agents and pathways that are most important to our understanding of how we treat and really think about developing new drugs for HR+ breast cancer. The first generation of anti-estrogen drugs really included selective estrogen receptor modulators, but now we have a new generation of these anti-estrogen drugs. And there's also orally administered selective estrogen receptor degraders, so-called SERDs, that we hope someday will be an alternative with already one approved for the injectable SERD, fulvestrant. But there's a whole additional class of drugs, complete estrogen receptor antagonists, referred to as CERANs, and proteolysis targeting chimerics, PROTACs. These agents are all at various stages of development in both early and metastatic settings and really represent, I think, a confusing array of different treatments that are being studied, some of which of course are approved. Nancy, it would be great if you could tell us some about these exciting new agents, starting with our approved drugs and moving on to the agents that we're studying in clinical trials. Dr. Nancy Davidson: Hope, this is a terrific example of how basic science has really begun to inform clinical practice. For us as breast cancer practitioners, it was really easy for a long time because we only had tamoxifen. And then things like the aromatase inhibitors as a means of decreasing the estrogen ligand came into practice, as did fulvestrant, as you mentioned, a selective estrogen receptor degrader. Thanks though to a lot of understanding about estrogen receptor biology, and specifically, the discovery about a decade ago of estrogen receptor mutations, something that we didn't think exist ed for a long time, but which we now know exists in maybe a third to a half of breast cancers after exposure to aromatase inhibitors, that's led to really an explosion, this alphabet soup of possibilities that you talked about. SERMs, selective estrogen receptor modulators, tamoxifen is the classic one—something that acts as an agonist and as an antagonist, depending on the tissue. The SERDs, the selective estrogen receptor degraders, lead to estrogen receptor destruction. Fulvestrant is the classic example of this right now. But we're very excited that a second one has been FDA approved. That's elacestrant that was approved earlier this year, and it has specifically been developed to try to target those estrogen receptor mutant breast cancers because those are the ones that are particularly resistant. So that's the first of this new generation of SERDs that's coming on the market, has come on the market. As you say, a key advantage there is that it's oral, unlike  fulvestrant, which requires 2 monthly injections and is very, very inconvenient and uncomfortable for patients. Other SERDs are coming along. I think another one that is well along in clinical development is giredestrant, which is in the same family and being tested in clinical trials of the classic varieties. It's been tested in a window trial, looking at its ability to down-regulate Ki67. It's being tested against standard of care in first-line metastatic breast cancer. And there are some studies that are going to begin looking at it in the adjuvant setting as well. There are other members of this particular family, but I think that elacestrant is the one that we have at our fingertips right now, and giredestrant is one that's certainly coming along in clinical trials, and we should look forward to those results. For those who are interested in the giredestrant, the trials in question right now that are going on are persevERA, which is in stage 4 breast cancer, and lidERA, which is in the adjuvant setting. Now that's one new category, or it's an old category with a new twist. A second is these agents that are called complete estrogen receptor antagonists, CERANs, as you talked about them. The key here is that what they do is, the estrogen receptor has a couple of domains, and in particular, it has 2 different activation domains, AFT1 and AFT2. And these CERANs are complete estrogen receptor antagonists, so they block both of those domains. And the hope would be that they might end up being more effective than the other agents that we have available to us right now. So those are also in clinical trial at the present time, and we're waiting to see whether or not there's going be any value in that particular area that's going to able to go forward for us.   Another area that I think we want to talk about is the PROTACs, as you mentioned. These are proteolysis targeting chimeric entities. So, this is a kind of a complicated situation where you have a kind of bivalent situation where you have something that binds both to the estrogen receptor and then also to E3 ubiquinase. So, it leads to degradation again of the agents; that's another area for us to be watching. And then finally the SERCAs. So those are the selective estrogen receptor covalent antagonists, and what they do is they bind very specifically to a cysteine 530 that exists in the estrogen receptor but not in other steroid receptors. So that's where the selective part of this comes along. Now these are all in various stages of clinical investigation. Some of them are pretty early at this point, but I think the ones that are well established are elacestrant, giredestrant is coming along as we just talked about. Camizestrant is also coming along through the SERENA series of trials, and imlunestrant is also coming on through the EMBER series of trials. Hope, I would also be remiss if I didn't go back to an old drug that's a new drug, and that's lasofoxifene, which is also in the SERM family. Those who have been in our field for a while will remember that lasofoxifene was actually originally kind of tested in the prevention setting, where it seemed to have some activity. It came back into our interest because it has really strong activity against estrogen receptor mutant breast cancer models in the laboratory. And as a consequence of that, it's coming back into the clinic through a series of trials that are called the ELAINE trials, where we're looking to see whether or not it might also be better than fulvestrant. It too is an oral agent, so that's a real plus for us, and the first set of ELAINE trials would suggest that there's some nice activity without a lot of toxicity. So, lots going on in this field. You know, I think for all of these things, obviously, we're also working very hard to think about the toxicities. All of these, as I recall, are oral agents. So that gets rid of  1 huge toxicity, which is you don't have the need for some sort of injection. But they all do have some side effects. Frequently, [the toxicities] are like GI side effects or fatigue. In a couple of cases, there might be some concern about cardiac arrhythmias, but I think GI turns out to be one of the most important things that we have seen in some of these trials. Generally, it's very well tolerated, though. I think another important question, which I'm sure is in your head and is in mine, is that how are we going to integrate these into what we already have? And so, I think a lot of the work right now is looking at patients who have already received an aromatase inhibitor plus a CDK4/6 inhibitor and are now going on to one of these new agents. But you might wonder, if they turn out to be effective and well-tolerated, whether they too should be perhaps combined with CDK4/6 inhibitors in place of the aromatase inhibitors or the fulvestrant that we use now. So, I think that we can imagine that those clinical trials are either in progress in some cases or will be coming on as we try to think about how to integrate these new approaches into our existing standard of care, which is already quite complicated, right? We've gone far from tamoxifen, which was good for everybody, to now a really complex algorithm about how we think about hormone therapy, both in early breast cancer and in metastatic breast cancer.  Dr. Hope Rugo: Well, that was a fabulous discussion about the new agents and our existing agents and both the exciting aspects, as well as the challenges. One question that comes up, I think a lot, and this is of course a huge question in many ways, but for ER-positive metastatic breast cancer, where these drugs are first being tested, maybe we'll talk about that first. There's one trial at SERENA-6, looking at camizestrant in patients who have developed evidence of an ESR1 mutation in circulating tumor DNA, who are on first-line therapy with an AI and a CDK4/6 inhibitor. What do you think about that study and where do you think that progress might go? Of course, that's based on data from another trial, which wasn't definitive, but suggested, had sort of a suggestion, you know, without studying the sequencing in detail that maybe you would have improved progression-free survival with that approach. Dr. Nancy Davidson: Yeah, by which you mean the idea of monitoring pre-ESR1 mutations and circulating DNA and then making therapy changes based on that? Is that what you're talking about? Dr. Hope Rugo:  The PADA-1 trial, yes, and that led to this huge SERENA-6 trial, which of course is now accruing. Dr. Nancy Davidson: So, you know, we would love that, right? I think that obviously breast cancer for many years has been interested in trying to have circulating markers that we could use to help to guide our therapy in a more meaningful way than we have in the past. And I think that the trial that you've talked about is certainly one that's trying to make that see whether that's a possibility for us based on information like the PADA trial. I'm hopeful it's going to work out. I would say, let's see what that looks like, whether it's going to be useful or not. It seems to me in some cases, some of these trials have not been quite what we hoped for, but I don't think we necessarily had the molecular techniques or the sensitivity, nor did we necessarily have other things to move to because, you know, those two approaches require both a really good test, but also the ability to use the test to define a new therapy that's going to lead to improved patient outcomes. And I think that these are ingredients that we now have available to us at our fingertips more than we did, say, a decade or 2 decades ago. Exciting approach. Dr. Hope Rugo:  I do think there's a lot of challenges inherent in this process, monitoring blood on a regular basis and following up and then randomizing based on results. But I think [SERENA-6] is an incredibly important trial, as you have mentioned, to try and think about moving past using circulating tumor cells, which didn't work, to just change blindly to the next therapy, but more have a rational reason to change to a drug that may be more effective before the disease itself progresses. And just for our listeners, the unique aspect of trials like this in SERENA-6 is that you change therapy before you have evidence of disease progression, but only this molecular evidence of a mutation that is associated with resistance to the therapy you're on. So, it's a really important question. We'll see what happens, as you mentioned, sometimes we're not clever enough to really get around the fact that there are multiple mutations driving resistance in this setting, so we'll see how straightforward this is. The question also comes up, and I think that's a question with many of these trials now, is they're randomizing patients after a progression on an AI and CDK4/6 inhibitor to receive the novel endocrine therapy or fulvestrant. One of, I think, the concerns of treating oncologists is that then you're sort of eliminating the possibility of a targeted agent in that setting. And of course, we have new targeted agents we're studying as well, AKT inhibitors and new inhibitors of the PI3 kinase pathway. So, the newer trials are now combining, as you mentioned. There's a lot of concerns about drug-drug interactions here and how you might really combine them. And then there are triplet studies looking at CDK4/6 inhibitors, oral SERDs primarily, and pi3-kinase and CDK4/6 inhibitors. What's your thought on these and will they really help to move the needle forward? Dr. Nancy Davidson: I think that's a really interesting question, Hope, is whether or not we're going to find that combination therapies from the get-go are the way to go, or whether we're going to end up having to use maybe more serial therapies. Because not only is it a question about whether or not you can tackle all of these different resistance mechanisms simultaneously, but I think the other question is, as you say, are there negative drug-drug interactions, and are there toxicities that are intolerable? Although these are targeted in all cases and they're relatively benign in terms of side effects from the breast cancer perspective, they're not devoid of toxicity. And so, I think that's going to be another issue for us – whether they're well tolerated during the time that patients are taking them. I guess the other thing I always think about, Hope,  is that it's hard to know about value of cancer care, but you know, we are talking about agents that are not inexpensive. You know, when you think about the financial toxicity, in addition to the side effect toxicity that you and I just talked about, trying to think about what that value is going to look like is going to be very important for us. Also, as somebody who worked for a long time in the lab and in the clinic, you know, there are an infinite number of combinations that you and I could think about that are rational. And so, the question is, how are we going to pick the ones that are the most rational, if you will, the ones that seem to be the most promising, and take them forward into clinical trials? Because patients are our most precious resource. And so, we want to make sure that we are bringing forward only those things that really seem to have a very strong foundation and the opportunity to improve outcomes over time. Tough, tough question for us to try to think about, as you've talked about. The other thing is that, you know, these trials are not only for postmenopausal women, who are the majority of patients, but we also want to target them to premenopausal women. So, in those women, we're also looking at using an LHRH agonist on top of this, right, because many of these things are really at least so far designed for the postmenopausal state. So stay tuned. Lots of work going on. I think one of the interesting things will be making the leap from using these in metastatic disease at time of progression to taking them forward into the early breast cancer space. And several of the agents are now beginning to do that because of very strong preclinical and clinical data to date. Dr. Hope Rugo: So, we have new agents that we're studying in the metastatic setting, and we've seen a trend to move fairly rapidly from phase 1B trials directly into phase 3 trials, because as you pointed out so clearly, there are a number of drugs in this setting, and we don't really know not only which agent is better, but even what class of agents is better. So, as we move more quickly from phase 1B to phase 3, the question comes up about how we're going to study these agents optimally in the early-stage setting. They, I think we all thought that maybe changing based on ctDNA evidence of a mutation might be an approach, but that's complicated. A big question for you is whether or not you think that's ready for prime time as it's being marketed as such. And then the second question is really, are we better changing our whole approach upfront in high-risk disease or should we wait until after patients are exposed to their endocrine therapy and then switch as we go along; the EMBER-4 trial is looking at that switching approach? Dr. Nancy Davidson: Yeah, I think that this is obviously the billion-dollar question for many companies and for many of us as investigators. I don't know that I have a crystal ball into what the best approach might be. We know that already some of these have been abandoned. For example, amcenestrant. So, I don't even have to learn how to say it because it has been abandoned. It did go to phase 3, as you pointed out, in the advanced setting, looking at it with palbo vs letrozole plus palbo, and it didn't really show a whole lot that the company wanted to pursue.  So, I think that sometimes these things are going to be abandoned based on the metastatic setting, which is a large trial, and that's a trial where obviously it might be a little easier to the circulating markers, as you talked about, than maybe in the early-stage breast cancer setting.  I think that probably these early-stage trials are going to end up being big; they're going to have be clean. I'm guessing that most companies and most investigators will want to target them towards high-risk individuals, as you talked about, for 2 reasons. One is that ethically, I think we feel more comfortable with that. These are individuals where standard therapies are maybe not serving them as well as we would like and where we have information to think that we can at least have equipoise about a new approach. And the second is that from a trial design point of view, the event rate is likely to be higher, and therefore you might get answers earlier and with a smaller clinical trial. So that's where I suspect we're going to go. But it's a challenging question, and I think that many investigators and many companies are really trying to struggle with that right now because we do have so many options. And we're not quite sure how to, first, develop these new drugs, but then really importantly, put them in the context of our existing drugs. And as you say, we're also simultaneously trying to develop superior molecular or circulating markers to guide us. So, there's so many variables that are going on right now in this field that, from my point of view, itmakes it really exciting, but it also makes it pretty complicated, both for investigators and for pharma as we try to think about how to position these going forward. But what a great problem to have, Hope, because remember when you and I started in breast cancer, pretty much all you needed to know was tamoxifen. And I think you and I also probably started at the tail end of the time when we were using androgens and progestins and agents that now have basically completely fallen out of favor. Dr. Hope Rugo: Estrogen Dr. Nancy Davidson: Estrogen, yeah, and your side effect profiles were not as good. So, it's a good problem to have. It's a nice situation when science can inform our clinical investigation, our clinical practice. Dr. Hope Rugo: Yes, I think it'll be fascinating to see where we end up at the end, but of course, the complexities of this include the fact that sometimes just the clinical trial design leads to a less than positive result because of the way the trial itself has been designed, which I think is the nice part about moving these earlier into treatment of high-risk disease, but also brings up the question of all sorts of areas we're not really a place to discuss today, like how the statistical design is made, et cetera, that can sometimes result in poor evaluation of excellent agents. One of the questions that comes up, and you brought this up earlier, which I think is really important, is that we are in the era of combining our endocrine agents with targeted agents, and, oral agents, in a fascinating way, really bring up drug-drug interactions in a way that the injectable fulvestrant hasn't, and aromatase inhibitors were kind of quiet on the impacting metabolism, unlike tamoxifen. But we are seeing some drug-drug interactions and certainly the discussions about using these agents may include the question about whether or not you're having more diarrhea or nausea or fatigue or one drug causes photopsia, flashing lights, things like that. Keratitis is becoming a new toxicity to follow.  How are we going to figure out how to sequence these drugs and are they only going to work better all of them as a class in patients with ESR1 mutations in their tumors? Dr. Nancy Davidson: I think we don't know the answer to the second question yet. That's something that really needs to be sorted out. Even if they do, that's still a really important subset of patients, assuming that we continue to start with the aromatase inhibitors, right? That's where those things really seem to emerge right now. I don't know how we're going to figure those things out. I guess that I'm hoping that maybe a couple of agents in these classes will become kind of the lead agents. And so, we'll be able to do this work with a handful of things as opposed to a whole array of things. But we'll see. I think that even within classes, obviously, these agents are going be slightly different, probably. And so it may be that one member of a class may be slightly better from a, maybe not from an efficacy point of view, but from a toxicity point of view. And we'll just have to see how it goes. I don't think I have any magic answers about that. Dr. Hope Rugo: Yes, it'll be interesting to see whether or not the agents work in sequence too. You know, could you use a PROTAC after an oral SERD, for example, or a CERAN? That'll be fascinating to see. Dr. Nancy Davidson:  I'm hoping that preclinical modeling may help with that a little bit, though of course we all know that there are plenty of things that do well in preclinical models, GEMS and rodent models and PDXs, and sometimes those things translate nicely into clinical practice, but sometimes they don't. Dr. Hope Rugo: You mentioned, Nancy, that when we started out, that it was a fairly simple decision about what endocrine therapies, and we ran out very quickly. We're seeing some of those old classes come up with new agents. And you mentioned lasofoxifene, the oral SERM that seems to have some benefits and works in the later-line setting and also can be combined with a CDK4/6 inhibitor; [and also] has data with abemaciclib. There's also a new androgen receptor agonist, enobosarm, that's being tested as well. Do you think that these older mechanisms have a future as well? Dr. Nancy Davidson: I do. I think that because we'll be able to understand the biology better than we did in the past. A lot of our hormone therapy was pretty empiric several decades ago. But I think with better understanding of mechanisms and better understanding of what the patterns of resistance might be for a particular tumor, that we might be able to think about those things. You're right that there's a whole parallel universe right now in androgen receptor targeted therapies that we're not talking about today, both in perhaps in hormone-responsive breast cancers, but also in triple-negative breast cancers in a certain subset. And so that's an area where we probably need to be watching what our prostate cancer colleagues are doing as they develop these agents and thinking about where they might mechanistically make sense to apply in the breast cancer field. It won't be the first time that we've received insights from them because remember, prostate cancer people knew about androgen receptor mutations a really long time before we figured out that they existed in estrogen receptor as well. So, there's a nice cross talk, I think, between the prostate cancer field and the breast cancer field in that regard. Dr. Hope Rugo:  That's an excellent point. And we learn a lot from our colleagues studying other malignancies, and prostate cancer has been a big area there for us and hopefully will help us with studying these agents because there's different toxicity profiles, of course, as well. And then you mentioned the approval of elacestrant, the first oral SERD to have regulatory approval, and it's approved in patients who have ESR1 mutations in their tumors. We're also studying it in the ELEVATE trial in combination with all of the different targeted agents, the CDK4/6 inhibitors, mTOR inhibitor, everolimus, and the PI3 kinase inhibitor, alpelisib, to really try and understand how these can be optimally combined. Would you check for ESR1 mutations at diagnosis of metastatic disease, or would you do this more after progression or start of progression of disease on an aromatase inhibitor? Dr. Nancy Davidson: I tend to be a conservative, Hope, and so unless there's a clinical trial that might be able to be considered, I would tend to check it only after progression on the aromatase inhibitor. But I think some people are earlier adopters, and I suppose it's possible that they might want to know from the get-go. Having said that, I do think elacestrant has an approval after aromatase inhibitor, as I recall. So, presumably the patient would have to have that exposure before you would be able to act on the ESR1 mutation by administering the oral SERD. This is also a new area that may well change with time, right? You know, as we develop different agents, as the agents have different requirements or different indications, and as we perhaps have better tests, it may be things that we don't do routinely now will become very routine in the future. And perhaps in series like you talked about in a serial fashion. Dr. Hope Rugo: Absolutely. I think that's a really important comment about how we're going to think about treating hormone receptor positive disease and potentially, you know, we have new chemo options, of course, not part of our talk discussion today and antibody drug conjugates. So, the future is certainly challenging in terms of understanding this appropriate sequencing. We need data, but it's exciting to have these options. As you pointed out, this is this is a great problem to have, you know, too many drugs with efficacy to try and understand how to use these in the most appropriate way. And as you also pointed out, the use in young women is particularly important. Whether or not you need to suppress the ovaries with all of these new agents is going to be important to understand as well as a next step. I don't know if you have specific thoughts on that area as well. I mean, that may reduce toxicity for younger women. Dr. Nancy Davidson: I guess our approach right now has been to suppress them, but I agree with you; you wonder if you look at some of the mechanisms of action, whether that's really a requirement biologically and medically, or whether it's something that's kind of a leftover from the approval process. You know, that for the drug approval, these women were suppressed. I think we need to work that out because that's another area where certainly women could have ovaries removed. That's pretty straightforward, although it requires a surgical procedure. But otherwise use of LHRH agonists continues to be injections, right? And so, if we're trying to minimize convenience or maximize convenience and minimize toxicity for women with any stage of breast cancer, anything we can do, it seems to me to eliminate an injection is going to be a good thing. So important for us to be able to work that out as well, even though numerically it's a smaller number of women, it's obviously a very important number. population of women. Dr. Hope Rugo: Last question for you. One question that comes up and sent to me and panels all the time is, if you have done your next generation sequencing and you see an ESR1 mutation and a P13CA mutation, what do you prioritize in terms of your choice of treatment, because we have the choice of either using elacestrant or a fulvestrant in combination with an agent targeting the PI3 kinase pathway? Dr. Nancy Davidson: I don't know that there's a right answer to that medically right now. So, when I talk about it with patients, I suggest to them that it's probably not one or the other. It's kind of the question of which one to use first. So, we talk a little bit about side effect profiles. We talk a little bit about patient preference and neither of these drugs is devoid of problems, but sometimes patients have pretty strong feelings about which set of side effects seems the least unattractive to them or the possibility of having those side effects. And I know that if one isn't well tolerated, you can swap over to the other. Dr. Hope Rugo: Absolutely. I think that's a very important way to think about next therapies in our era of not really knowing what's right. And this idea of shared decision-making is so incredibly important. Nancy, thank you so much for sharing your insights and knowledge with us today. I could talk to you for hours about this. Dr. Nancy Davidson: Hope, thank you so much for the opportunity. It is an exciting area and I really enjoyed talking with you about what we know and the many things that we don't yet know, but we're working on. Dr. Hope Rugo: Indeed, it's certainly an exciting time. Thank you to our listeners for joining us today. And thanks to the ASCO Daily News Podcast for highlighting this important area. You'll find a link to all of the studies discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thanks so much.   Disclaimer:    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Follow today's speakers:     Dr. Hope Rugo  @hoperugo  Dr. Nancy Davidson     Follow ASCO on social media:     @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:     Dr. Hope Rugo:  Consulting or Advisory Role: Napo Pharmaceuticals, Puma Biotechnology, Mylan, Eisai, Daiichi Sankyo Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Astellas Pharma, Talho Oncology, Veru, GlaxoSmithKline, Hoffmann-LaRoche AG/Genentech, Inc Travel, Accommodations, Expenses: Merck, AstraZeneca   Dr. Nancy Davidson: No Relationships to Disclose    

Ishayu Chakroborty '24 was chosen as one of Mobile Bay's 2023 WONDER KIDS. During Project Engage Ish chose to do an internship with Dr. Grelet in the Department of Biochemistry and Molecular Biology at Mitchell Cancer Institute. Dr. Grelet specializes in tumor neurogenesis in cancer progression and metastasis with a focus on breast cancer. During the internship with Dr. Grelet, he was able to observe and assist with experimental lab work, as well as learn about bioinformatics and data analysis in biology, especially in breast cancer. The experience during Project Engage sparked his interest in cancer research and drove him to learn further about data analysis from publicly available datasets and repositories. The findings then led to a research project with guidance from Dr. Kakkat Ph.D. in the Department of Pathology at the Mitchell Cancer Institute. Because of his dedicated work in the research lab at the Mitchell Cancer Institute, Ish registered as a member of the American Association for Cancer Research (AACR) in the spring of 2022 and was invited to attend the AACR 2022 annual meeting in New Orleans [AS A JUNIOR IN HIGH SCHOOL!]. The American Association for Cancer Research (AACR) is the first and largest cancer research organization dedicated to accelerating the conquest of cancer. He then was contacted by Dr. Robin Felder, Director of Membership and Professional Development for AACR to complete the student registration form to attend the Special Program for High School Students entitled, "The Conquest of Cancer and the Next Generation of Cancer Researchers." He was then approached to present his research. Before Ish knew it, he had been vetted for membership and submitted the title of his research proposal for approval! American Association for Cancer Research had over 20,000 in attendance and Ish was ONE of only seven students in the United States who were invited to present their work/research at the meeting.

This week on The Less Stressed Life Podcast, I am joined by Dr. Barrie Tan. In this episode, we get SUPER NERDY about types of Vitamin E. Dr. Tan sources Vitamin E from annatto, the stuff that colors your cheese yellow and is from a tree in South America. Since I had just returned from South America right before recording this episode, we hit it off talking about Incan cultural uses of annatto. Just a day in my dream life of being a podcaster. KEY TAKEAWAYS:Cell membranes (which actually applies to you if you have ANY condition, deficiency or dry skin)Fatty liver disease, lipids, inflammation, weight loss, cancer and the impact of specific types of Vitamin ETocotrienols and sources from palm, rice and annatto and protecting the antioxidant from oxidation (making it anti-healthy). ABOUT GUEST:Dr. Barrie Tan is hailed as a trailblazer and the world's foremost expert on vitamin E. A scientist first and foremost, Dr. Tan earned his Ph.D. in Chemistry/Biochemistry from the University of Otago, New Zealand and spent several years as a professor at UMass. His research expertise includes lipid-soluble nutrients (carotenoids, E vitamers, CoQ10, and omega-3s) that impact chronic conditions. He was the first to introduce tocotrienols benefits to the nutrition industry and developed the first-ever tocopherol-free tocotrienol product derived from annatto. Dr. Tan continues to collaborate with numerous universities worldwide to further tocotrienol research. Beyond tocotrienol, Dr. Tan's research now spans into geranylgeraniol, a critical endogenous nutrient for healthy aging.Dr. Tan has held roles of Chief Scientific Officer and Scientific Board Member for multinational organizations. His career includes periods working in association with the US Armed Forces and a Prince of Thailand as well as being an internationally celebrated and sought-after speaker, having presented at multiple respected conferences in the field including; IFT, ADA, ASN, IHS, A4M, NPA, AACR, ICIM, AOCS, IAOMT, and the Academy of Nutrition and Dietetics. Renowned for his engaging warmth and gracious humor, Dr. Tan has also been featured in array of popular media including the Ben Greenfield and JJ Virgin podcasts.Dr. Tan is currently the President of American River Nutrition, a natural health R&D company he started with his wife, Elizabeth, in 1998. Described as a scientific pioneer, his mission is simple, improve the everyday health of people's lives.WHERE TO FIND:Website: https://barrietan.com/Instagram: https://www.instagram.com/doctorbarrietan/Facebook: https://www.facebook.com/doctorbarrietanLinked In: https://www.linkedin.com/in/dr-barrie-tan/WHERE TO FIND CHRISTA:Website: https://www.christabiegler.com/Instagram: instagram.com/anti.inflammatory.nutritionist/Leave a review, submit a questions for the podcast or take one of my quizzes here: https://www.christabiegler.com/links