Podcasts about Immunotherapy

As lung cancer treatments become more complex, is a collaborative tumor board more essential than ever? We're kicking off the 2025 NSCLC Creator Weekend™ series with an in-studio panel discussion on the multidisciplinary management of lung cancer. The panel includes experts from medical oncology, thoracic surgery, radiation oncology, and interventional pulmonology from major institutions in Los Angeles. --- This podcast is supported by an educational grant from Johnson & Johnson and Varian. --- SYNPOSIS They discuss the operation of tumor boards at their respective institutions, the impact of virtual meetings, optimal strategies for mediastinal staging, the management of early-stage lung cancer, and the emerging role of ablation therapy. The conversation dives into the complexities of treating patients with recurrence or metastatic disease, highlighting the importance of collaborative decision-making in navigating these challenging scenarios. The episode emphasizes the critical role of multidisciplinary tumor boards in providing informed, patient-centered care. --- TIMESTAMPS 00:00 - Introduction06:59 - Role of Pulmonologists in Tumor Boards12:08 - Importance of Tissue Diagnosis24:52 - Lung Cancer Screening and Stigma34:01 - Interventional Radiology and Biopsies46:21 - Challenges with Immunotherapy and Radiation53:44 - The Importance of Multidisciplinary Teams54:24 - Final Thoughts --- RESOURCES American Lung Association 2024 Datahttps://www.lung.org/getmedia/12020193-7fb3-46b8-8d78-0e5d9cd8f93c/SOLC-2024.pdf National Lung Screening Trialhttps://www.nejm.org/doi/full/10.1056/NEJMoa1102873 Checkmate 816https://www.nejm.org/doi/full/10.1056/NEJMoa2202170 PACIFIC Trialhttps://www.nejm.org/doi/full/10.1056/NEJMoa1709937

A breakthrough that could reshape cancer treatment.GT Biopharma (NASDAQ: GTBP) is advancing its next generation TriKE® platform, an innovative immunotherapy that activates the body's own natural killer cells to identify and destroy cancer. In this interview, Executive Chairman & CEO Michael Breen discusses the company's latest clinical progress and the potential of its lead drug candidate, GTB-3650.He also shares insights into the science behind TriKE®, the company's pipeline for solid tumors and autoimmune diseases, and its mission to develop more humane cancer therapies that bring real hope to patients worldwide.Learn more about GT Biopharma: https://www.gtbiopharma.com/Watch the full YouTube interview here: https://youtu.be/jduKYNKHMIYAnd follow us to stay updated: https://www.youtube.com/@GlobalOneMedia

You've probably heard of Oral Immunotherapy—or OIT—a treatment that's gaining attention in the food allergy world. But what's it really like to go through the process? Many families discover there's more to OIT than they expected. To help unpack the basics and offer clarity, we're talking with allergist, Dr. Brian Vickery, about what to know before beginning this journey. Resources to keep you in the know:Resources to keep you in the know:FAACT's Food Allergy Treatments SectionFAACT's Navigating Treatment Choices Section FAACT's Navigating the Food Allergy Treatment Decision ProcessYou can find FAACT's Roundtable Podcast on Apple Podcasts, Pandora, Spotify, Podbay, iHeart Radio, or wherever you listen to podcasts.Follow us on Facebook, Instagram, BlueSky, Threads, LinkedIn, Pinterest, TikTok, and YouTube.Sponsored by: Stallergenes GreerThanks for listening! FAACT invites you to discover more exciting food allergy resources at FoodAllergyAwareness.org!

EPISODE DESCRIPTION:Libby Amber Shayo didn't just survive the pandemic—she branded it. Armed with a bun, a New York accent, and enough generational trauma to sell out a two-drink-minimum crowd, she turned her Jewish mom impressions into the viral sensation known as Sheryl Cohen. What started as one-off TikToks became a career in full technicolor: stand-up, sketch, podcasting, and Jewish community building.We covered everything. Jew camp lore. COVID courtship. Hannah Montana. Holocaust comedy. Dating app postmortems. And the raw, relentless grief that comes with being Jewish online in 2025. Libby's alter ego lets her say the quiet parts out loud, but the real Libby? She's got receipts, range, and a righteous sense of purpose.If you're burnt out on algorithm-friendly “influencers,” meet a creator who actually stands for something. She doesn't flinch. She doesn't filter. And she damn well earned her platform.This is the most Jewish episode I've ever recorded. And yes, there will be guilt.RELATED LINKSLibby's Website: https://libbyambershayo.comInstagram: https://www.instagram.com/libbyambershayoTikTok: https://www.tiktok.com/@libbyambershayoLinkedIn: https://www.linkedin.com/in/libby-walkerSchmuckboys Podcast: https://jewishjournal.com/podcasts/schmuckboysForbes Feature: Modern Mrs. Maisel Vibes https://www.forbes.com/sites/joshweissMedium Profile: https://medium.com/@libbyambershayoFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform.For guest suggestions or sponsorship, email podcast@matthewzachary.com.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

When treating head and neck cancer, how can you tell the difference between true disease progression and pseudoprogression? In this episode of the BackTable Podcast, we discuss the practical implementation of the KEYNOTE-689 trial published in the New England Journal of Medicine, which demonstrated the benefit of adding neoadjuvant and adjuvant immunotherapy to standard head and neck cancer care. Our tumor board panel includes Dr. Mihir Patel, a head and neck surgeon from UNC Chapel Hill, Dr. Siddharth Sheth, a head and neck medical oncologist from UNC, Dr. Jennifer Johnson, a professor of medical oncology and otolaryngology at Sidney Kimmel Comprehensive Cancer Center, and Dr. Adam Luginbuhl, a head and neck surgical oncologist at Thomas Jefferson University. --- SYNPOSIS The doctors address the trial's practical implications, patient selection, case management, dealing with tumor progression, and the integration of multidisciplinary care. They also emphasize the importance of communication, real-world application of trial protocols, and the potential benefits and challenges of such therapies. --- TIMESTAMPS 00:00 - Introduction03:18 - Discussing the New Indication for Immunotherapy11:42 - Challenges and Practical Implementation22:48 - Managing Tumor Progression: A Case Study28:07 - Exploring Treatment Options: Surgery vs. Chemotherapy36:46 - Operational Challenges and Future Directions43:58 - Concluding Thoughts and Future Directions --- RESOURCES Keynote 689https://www.nejm.org/doi/full/10.1056/NEJMoa2415434

On Tuesday's show: Children at Risk has released its annual list of the top public schools in Houston. The organization's CEO, Bob Sanborn, walks us through the rankings.Also this hour: Houstonians played a big role in the Gemini missions, which were stepping stones in America's 1960s journey to the moon. The program that preceded Apollo is the focus of Jeffrey Kluger's new book, Gemini: Stepping Stone to the Moon, the Untold Story.Then, we visit Texas Children's Hospital to learn about the first immunotherapy center dedicated to fighting pediatric cancer.And, on Veterans Day, we hear local Air Force veteran Ty Mahany's story about an encounter with a World War II veteran and discover what he learned about engaging fellow veterans in conversations about their service.Watch

Send us a textIs your lab truly digitally ready—or just scanning slides?That's the question I unpack in this live discussion from Day 2 of SITC's 40th Anniversary Meeting, joined by David Anderson (Biocare Medical) and Don Ariyakumar (Hamamatsu Photonics). Together, we explore what digital readiness really means for multiplex immunofluorescence (mIF) and how to build reliable, reproducible workflows that scale from research to clinical settings.What We DiscussThe Discovery Funnel I open by situating mIF within the broader discovery funnel: researchers begin with hundreds of biomarkers, narrowing down to focused 4–10 marker panels where true clinical utility begins. But this only works if the lab is digitally prepared from the start—from slide prep to data capture.Defining Digital Readiness David Anderson reframes digital readiness as everything that happens before the scanner turns on:Reagent consistencyAntibody optimizationAutomationStandardized protocols All these elements ensure that downstream AI and image analysis tools work on clean, reproducible data instead of “fixing” noise later.The Pre-Analytical Foundation Don Ariyakumar emphasizes that scanning can't fix variability. If staining or section quality isn't standardized, digitization simply amplifies inconsistencies. True readiness starts at the bench, not the monitor.Integration Across Vendors We also talk about how interoperability between stainers, scanners, and spatial biology software is becoming essential. A disconnected workflow—mixing manual, unaligned steps—adds variables that no algorithm can fully normalize.Lessons from IHC's Evolution The team draws parallels between multiplex IF today and IHC's early days: once complex, now routine. Multiplex IF promises even richer tumor microenvironment insights, but only if standardization and automation catch up to the technology.Beyond the Funnel I revisit the “funnel” metaphor in a new light—arguing that as precision medicine grows, the bottom of the funnel broadens, not narrows. That means more tailored, smaller panels rather than one-size-fits-all assays, and a growing need for efficient, reproducible digital workflows.Key Takeaways“Digital readiness” starts before scanning — with chemistry, automation, and process control.Consistent pre-analytical quality = reproducible, AI-ready data.Interoperability between systems (like Biocare's ONCORE Pro X and Hamamatsu's MoxiePlex) accelerates workflow standardization.Multiplex IF is maturing quickly, just as IHC once did—on its way to becoming a cornerstone of precision pathology.Resources Mentioned

In this episode of the Wise Divine Women podcast, Dana Irvine and Dr. John Oertle discuss the latest advancements in breast cancer research, focusing on recurrence rates, the role of circulating tumor cells, and the importance of optimizing the immune system. Dr John's main goal is to enlighten Americans and people worldwide that there is a groundbreaking study published in Nature is shining a light on a hidden risk: respiratory infections can reawaken dormant breast cancer cells, accelerating recurrence. Read the article and research links They explore the impact of environmental toxins on cancer, the necessity of early detection through testing, and the effects of respiratory infections on cancer patients. The conversation also touches on the role of vaccines in immune response and the potential future of peptides in cancer treatment, emphasizing the need for advocacy in accessing innovative therapies.Envita Medical Center Want to listen to our first episode together? Wise Divine Women podcast, host Dana Irvine speaks with Tammy Morrow and Dr. John Oertle about the intersection of faith, health, and innovative cancer treatmentsTakeawaysRecurrence rates for stage one breast cancer can be as high as 20-30%.Circulating tumor cells can be detected even in early-stage cancers.Optimizing the immune system is crucial for cancer patients.Environmental toxins may trigger cancer development.Testing for circulating tumor cells can aid in early detection.Respiratory infections can impact cancer recurrence and growth.Vaccines may enhance immune response in cancer treatment.Peptides show promise in cancer treatment but require careful dosing.Advocacy for access to innovative treatments is essential.Education and awareness are key for patients in managing their health.Chapters00:00 Introduction to Breast Cancer Research01:04 Understanding Recurrence Rates in Breast Cancer03:51 The Role of Circulating Tumor Cells09:38 Maximizing Outcomes Through Immune System Support17:18 Challenges in Oncology: Insurance and Testing21:20 Environmental Toxins and Cancer Prevention23:43 Impact of Respiratory Infections on Cancer25:15 The Role of IL-6 in Cancer Growth28:25 Monitoring Cancer Recurrence Post-Infection29:37 Vaccines and Immune Response33:14 Immunotherapy and Immune System Dynamics37:45 The Future of Peptides in Cancer Treatment46:05 Access to Preventive HealthcareI hope you enjoyed this episode! Please leave a review and share with friends and family Want to learn more about my offerings? Please visit danairvine.com I invite you to schedule a Soul Session to lern about how we can work together or dive right in and book a Women's Hormone Transformation

Send us a textCan spatial biology and multiplex immunofluorescence truly transform how we understand cancer?I went live from the Society for Immunotherapy of Cancer (SITC) 2025 — the 40th Anniversary Meeting to explore how spatial biology, multiplex IF, and digital pathology are coming together to redefine cancer diagnostics, research, and precision medicine.This session kicked off a weekend of cutting-edge discussions with leaders from Hamamatsu (Booth 415) and Biocare Medical (Booth 717) — two companies helping laboratories around the world embrace digital transformation and spatial imaging in oncology.

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When the system kills a $2.4 million study on Black maternal health with one Friday afternoon email, the message is loud and clear: stop asking questions that make power uncomfortable. Dr. Jaime Slaughter-Acey, an epidemiologist at UNC, built a groundbreaking project called LIFE-2 to uncover how racism and stress shape the biology of pregnancy. It was science rooted in community, humanity, and truth. Then NIH pulled the plug, calling her work “DEI.” Jaime didn't quit. She fought back, turning her grief into art and her outrage into action. This episode is about the cost of integrity, the politics of science, and what happens when researchers refuse to stay silent.RELATED LINKS• The Guardian article• NIH Grant• Jaime's LinkedIn Post• Jaime's Website• Faculty PageFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship email podcasts@matthewzachary.comSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Dr. Elias Sayour, a pediatric hematologist and oncologist, joins Lester Kiewit to discuss research suggesting that Pfizer and Moderna mRNA COVID-19 vaccines can enhance the effectiveness of immunotherapy in some cancer patients. Dr. Sayour explains that when administered within 100 days of starting checkpoint inhibitor treatment, the vaccines “act like a 911 siren,” mobilizing immune cells to better target tumors, with evidence observed across cancers including lung, melanoma, breast, and head and neck cancers. While the findings are retrospective and not yet definitive, Dr. Sayour highlights the potential for future trials and the broader promise of mRNA technology in cancer therapy, universal vaccines, and personalized immune responses. “Even if we run a phase three trial and it doesn’t work, it is my sincere belief that this idea holds merit,” he says. Good Morning Cape Town with Lester Kiewit is a podcast of the CapeTalk breakfast show. This programme is your authentic Cape Town wake-up call. Good Morning Cape Town with Lester Kiewit is informative, enlightening and accessible. The team’s ability to spot & share relevant and unusual stories make the programme inclusive and thought-provoking. Don’t miss the popular World View feature at 7:45am daily. Listen out for #LesterInYourLounge which is an outside broadcast – from the home of a listener in a different part of Cape Town - on the first Wednesday of every month. This show introduces you to interesting Capetonians as well as their favourite communities, habits, local personalities and neighbourhood news. Thank you for listening to a podcast from Good Morning Cape Town with Lester Kiewit. Listen live on Primedia+ weekdays between 06:00 and 09:00 (SA Time) to Good Morning CapeTalk with Lester Kiewit broadcast on CapeTalk https://buff.ly/NnFM3Nk For more from the show go to https://buff.ly/xGkqLbT or find all the catch-up podcasts here https://buff.ly/f9Eeb7i Subscribe to the CapeTalk Daily and Weekly Newsletters https://buff.ly/sbvVZD5 Follow us on social media CapeTalk on Facebook: https://www.facebook.com/CapeTalk CapeTalk on TikTok: https://www.tiktok.com/@capetalk CapeTalk on Instagram: https://www.instagram.com/ CapeTalk on X: https://x.com/CapeTalk CapeTalk on YouTube: https://www.youtube.com/@CapeTalk567See omnystudio.com/listener for privacy information.

Dr. Stacy Lindborg, President and CEO of IMUNON, has developed a DNA-based immunotherapy candidate for the treatment of ovarian cancer. This therapy works by administering the drug, which utilizes IL-12, a powerful anti-cancer cytokine, directly into the cavity where the cancer resides, thereby affecting the tumor microenvironment. Trials are showing that the drug can produce significant life extension when used in combination with standard chemotherapy. Stacy explains, "There are about 300,000 women who are newly diagnosed with advanced ovarian cancer every year, about 20,000 in the US, and the frontline standard of care hasn't seen a change in the treatment in about 25 years. So this is for newly diagnosed women. The very first treatment that they would have, which we call frontline treatment, is a platinum-based chemotherapy. So carboplatin and Paclitaxel are both administered through IV over an hour for carboplatin, about three hours for Paclitaxel. So most women go directly to chemotherapy and then surgery, and then chemotherapy. Some women will go straight to surgery and then have this chemotherapy afterwards."   "Our approach is a DNA-based immunotherapy candidate that we have in Phase 3. We refer to the lead candidate as IMNN-001, and this is a non-viral nanoparticle that is administered directly into the cavity of interest. So, what we call the micro-tumor environment is the peritoneal cavity, where the cancer actually resides, and it's delivered through a catheter. And it basically has a very powerful anti-cancer fighting cytokine, IL-12, that is encoded in this immunotherapy. And it causes the cells that are within each woman's body, both cancer and non-cancer alike, to start producing activities that will help fight these complex cancer cells that exist."  #IMUNON #OvarianCancer #DNABasedImmunotherapy #WomensHealth #CancerAwareness  imunon.com Listen to the podcast here

Dr. Stacy Lindborg, President and CEO of IMUNON, has developed a DNA-based immunotherapy candidate for the treatment of ovarian cancer. This therapy works by administering the drug, which utilizes IL-12, a powerful anti-cancer cytokine, directly into the cavity where the cancer resides, thereby affecting the tumor microenvironment. Trials are showing that the drug can produce significant life extension when used in combination with standard chemotherapy. Stacy explains, "There are about 300,000 women who are newly diagnosed with advanced ovarian cancer every year, about 20,000 in the US, and the frontline standard of care hasn't seen a change in the treatment in about 25 years. So this is for newly diagnosed women. The very first treatment that they would have, which we call frontline treatment, is a platinum-based chemotherapy. So carboplatin and Paclitaxel are both administered through IV over an hour for carboplatin, about three hours for Paclitaxel. So most women go directly to chemotherapy and then surgery, and then chemotherapy. Some women will go straight to surgery and then have this chemotherapy afterwards."   "Our approach is a DNA-based immunotherapy candidate that we have in Phase 3. We refer to the lead candidate as IMNN-001, and this is a non-viral nanoparticle that is administered directly into the cavity of interest. So, what we call the micro-tumor environment is the peritoneal cavity, where the cancer actually resides, and it's delivered through a catheter. And it basically has a very powerful anti-cancer fighting cytokine, IL-12, that is encoded in this immunotherapy. And it causes the cells that are within each woman's body, both cancer and non-cancer alike, to start producing activities that will help fight these complex cancer cells that exist."  #IMUNON #OvarianCancer #DNABasedImmunotherapy #WomensHealth #CancerAwareness  imunon.com Download the transcript here

EPISODE DESCRIPTIONAllison Applebaum was supposed to become a concert pianist. She chose ballet instead. Then 9/11 hit, and she ran straight into a psych ward—on purpose. What followed was one of the most quietly revolutionary acts in modern medicine: founding the country's first mental health clinic for caregivers. Because the system had decided that if you love someone dying, you don't get care. You get to wait in the hallway.She's a clinical psychologist. A former dancer. A daughter who sat next to her dad—legendary arranger of Stand By Me—through every ER visit, hallway wait, and impossible choice. Now she's training hospitals across the country to finally treat caregivers like patients. With names. With needs. With billing codes.We talked about music, grief, psycho-oncology, the real cost of invisible labor, and why no one gives a shit about the person driving you to chemo. This one's for the ones in the waiting room.RELATED LINKSAllisonApplebaum.comStand By Me – The BookLinkedInInstagramThe Elbaum Family Center for Caregiving at Mount SinaiFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship, email podcast@matthewzachary.com.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

We are incredibly excited to host Dr. Chaudhry for our October Huddle, where he will dive into the latest advancements in stem cell research for Type 1 Diabetes, including updates from trials taking place right here in Vancouver. He will also share insights into upcoming immunotherapy trials aimed at delaying or preventing the progression of T1D, with recruitment beginning this Fall.Don't miss this opportunity to hear from a leading researcher about the cutting-edge science shaping the future of diabetes care and to ask your questions about what's next in T1D treatment and innovation.Over 18 and interested in sharing your experiences living with type 1? Register to attend a live huddle at www.t1dhuddle.com

In this podcast, Dr David Miller, MD, PhD, FAAD and Dr Vishal Patel, MD discuss the evolving treatment landscape and immunotherapeutic strategies for cutaneous squamous cell carcinoma (cSCC) based on key data from pivotal studies that are reshaping standards of care, including:Trials of neoadjuvant immunotherapies demonstrating remarkable response rates with PD-(L)1 inhibitors such as cemiplimab, pembrolizumab, atezolizumab, and nivolumab with or without ipilimumabOngoing investigational efforts, including the phase III CLEAR CSCC study of intralesional immunotherapy and radiation-immunotherapy sequencingPresenters:David M. Miller, MD, PhD, FAADDirector, Center for Merkel Cell CarcinomaCo-Director, NMSC Multi-Disciplinary ClinicMassachusetts General Cancer CenterAssistant Professor of Medicine and DermatologyHarvard Medical SchoolBoston, MassachusettsVishal Anil Patel, MDDirector of Cutaneous Oncology, GW Cancer CenterDirector of Dermatologic Surgery, GW Department of DermatologyAssociate Professor of Dermatology & of Medicine (Hematology/Oncology)George Washington University School of Medicine & Health SciencesWashington, DCLink to full program: https://bit.ly/3JbflO3 Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Phil L'Huillier, CEO of Scancell, has developed an off-the-shelf DNA immunotherapy designed to generate a potent and durable immune response against advanced melanoma in patients who are unresponsive to current therapies. Their lead candidate showed significant benefit when added to standard of care checkpoint inhibitors, improving duration of response without adding side effects or toxicity. Patient selection in future trials will use a blood test to identify the immune types that can be expected to respond best to the therapy. Phil explains, "Perhaps first and foremost, Scancell is a clinical-stage company developing novel active immunotherapies for patients. And our objective for patients is to pick up the patients that are unresponsive to current therapies or that respond for a short period of time to improve the overall survival through developing therapies that give a good duration of response, potent immune responses, but are also safe for patients." "Perhaps before I share results from the studies, I should step back a little bit and just tell you about the platform and the product that the data has arisen for. At Scancell, we're developing these off-the-shelf. The data that we're about to talk about comes from our lead program, which is an off-the-shelf DNA immunotherapy called Immunobody, that's the name that we use for it. And it's different from the personalized therapies, the personalized vaccines that require an individual to give a tumor sample. And then there's sequencing and manufacturing for the individual there. This is off the shelf." #Scancell #Immunobody #Immunotherapy #Cancer #Oncology #Melanoma #Biotech scancell.co.uk Download the transcript here

Phil L'Huillier, CEO of Scancell, has developed an off-the-shelf DNA immunotherapy designed to generate a potent and durable immune response against advanced melanoma in patients who are unresponsive to current therapies. Their lead candidate showed significant benefit when added to standard of care checkpoint inhibitors, improving duration of response without adding side effects or toxicity. Patient selection in future trials will use a blood test to identify the immune types that can be expected to respond best to the therapy. Phil explains, "Perhaps first and foremost, Scancell is a clinical-stage company developing novel active immunotherapies for patients. And our objective for patients is to pick up the patients that are unresponsive to current therapies or that respond for a short period of time to improve the overall survival through developing therapies that give a good duration of response, potent immune responses, but are also safe for patients." "Perhaps before I share results from the studies, I should step back a little bit and just tell you about the platform and the product that the data has arisen for. At Scancell, we're developing these off-the-shelf. The data that we're about to talk about comes from our lead program, which is an off-the-shelf DNA immunotherapy called Immunobody, that's the name that we use for it. And it's different from the personalized therapies, the personalized vaccines that require an individual to give a tumor sample. And then there's sequencing and manufacturing for the individual there. This is off the shelf." #Scancell #Immunobody #Immunotherapy #Cancer #Oncology #Melanoma #Biotech scancell.co.uk Listen to the podcast here

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/CPY865. CME/AAPA credit will be available until October 20, 2026.The Immunotherapy Story Continues for CSCC: Insights and Evidence on Advances in Resectable and Unresectable Disease In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/CPY865. CME/AAPA credit will be available until October 20, 2026.The Immunotherapy Story Continues for CSCC: Insights and Evidence on Advances in Resectable and Unresectable Disease In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/AAPA information, and to apply for credit, please visit us at PeerView.com/CPY865. CME/AAPA credit will be available until October 20, 2026.The Immunotherapy Story Continues for CSCC: Insights and Evidence on Advances in Resectable and Unresectable Disease In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

Professor Aideen Ryan, Professor in Tumour Immunology at University of Galway's College of Medicine, Nursing and Health Sciences. Photo: Andrew Downes Researchers at the University of Galway have revealed the results of a world-first study into how bowel cancer shuts down the immune system, and how this can be reversed to improve treatment. The findings have been published in the Journal for ImmunoTherapy of Cancer (JITC). Breakthrough for bowel cancer immunotherapy The research team showed how structural stromal cells switch off the immune system and how the body's own killer cells can be switched back on, opening up the opportunity for a completely new approach to optimising immunotherapy for patients. Colorectal cancer - commonly referred to as bowel cancer - is one of the world's most common cancers and the second leading cause of cancer death worldwide. Diagnoses in people under 50 have been climbing in recent decades, with recent global analysis showing these early-onset cases have almost doubled since 1990. In Ireland, the disease affects more than 2,500 people a year. Professor Aideen Ryan, Professor in Tumour Immunology at University of Galway's College of Medicine, Nursing and Health Sciences, said: "While immunotherapy has revolutionised care in cancers such as melanoma and lung cancer, it has shown very limited benefit in bowel cancer, leaving patients with advanced disease with few treatment options and poor survival outcomes." The breakthrough research discovery is the first to demonstrate that tumour stromal cells - the structural cells that support cancer growth - are directly reprogramming the immune system. They do this by switching off, or hijacking, two of our body's most important tumour-fighting cells - the natural killers (NK) and macrophages - rendering them unable to attack the cancer. Professor Ryan said: "The interaction between the cancer, our body's healthy cells and our defence mechanism is a complex one, but our research shows that the cancer is essentially creating an immune brake - it is blocking the body's natural response and fight mechanism." What has been discovered in relation to how the cancer interacts with the human body? Tumour stromal cells are the structural cells which allow the cancer to grow. They are coated in sugars called sialoglycans. These interact with receptors on the body's immune cells called Siglecs. This interaction causes the body's natural defence response to be switched off and unresponsive when immunotherapy is used, and therefore unable to attack the cancer. The research identified a specific enzyme that drives this process of 'switching off', as it produces the Siglec-binding sugars on stromal cells. When the researchers blocked this pathway using drugs called sialidases, they could show that the body's most important tumour-fighting cells - the natural killers (NK) and macrophages - reactivated. It showed that the tumours shrank and the spread of cancer, known as metastasis, was prevented. The multidisciplinary research was conducted in collaboration with colorectal surgeons and pathologists at Galway University Hospital, led by Professor Aisling Hogan and Professor Sean Hynes; as well as experts in colorectal cancer - Dr Philip Dunne, Queen's University Belfast and experts in targeting sialoglycans at Palleon Pharmaceuticals, MA, USA, who have developed sialidase drugs that disrupt the sialoglycan-Siglec interaction. Professor Ryan added: "Our research is a clear breakthrough in our understanding of bowel cancer and how immunotherapy could be more successful. This world-first finding shows that some of the bowel cancer cells are not just passive bystanders, they are actively reprogramming the body's immune cells, preventing them from doing their job. We have uncovered an entirely new checkpoint and by focusing on it we can reactivate the immune system and improve our body's innate ability to fight the disease, and even target metastasis." Michael O'Dwyer, Pro...

EPISODE DESCRIPTIONRebecca V. Nellis never meant to run a nonprofit. She just never left. Twenty years later, she's still helming Cancer and Careers after a Craigslist maternity-leave temp job turned into a lifelong mission.In this 60-minute doubleheader, we cover everything from theater nerdom and improv rules for surviving bureaucracy, to hanging up on Jon Bon Jovi, to navigating cancer while working—or working while surviving cancer. Same thing.Rebecca's path is part Second City, part Prague hostel, part Upper East Side grant writer, and somehow all of that makes perfect sense. She breaks down how theater kids become nonprofit lifers, how “sample sale feminism” helped shape a cancer rights org, and how you know when the work is finally worth staying for.Also: Cleavon Little. Tap Dance Kid. 42 countries. And one extremely awkward moment involving a room full of women's handbags and one very confused Matthew.If you've ever had to hide your diagnosis to keep a job—or wanted to burn the whole HR system down—this one's for you.RELATED LINKSCancer and CareersRebecca Nellis on LinkedIn2024 Cancer and Careers Research ReportWorking with Cancer Pledge (Publicis)CEW FoundationI'm Not Rappaport – Broadway InfoFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship opportunities, email podcast@matthewzachary.com.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Want to heal your child's eczema without steroids and save $200 this week? Click here to get started → EczemaKids.com Use code EPISODE200 to get $200 off the Eczema Elimination Method.... the COMPLETE eczema-reversal system that actually works. This offer is good for one week only and ends Tuesday, November 4th, 2025. If your child's ever had an allergy test hoping for answers, only to walk out more confused or flaring, this episode is for you. As we celebrate 200 episodes (and my birthday week!), I'm breaking down what allergy tests actually measure, why kids with eczema often react badly, and how to tell the difference between true, serious IgE allergies and immune overload. We'll talk about why scratch tests and immunotherapy often do more harm than good for eczema families, what to do if your child already flared after testing, and how to start healing their skin and gut from the inside out.

While the standard for adjuvant head and neck cancer treatment hasn't changed since 2004, a new trial using perioperative pembrolizumab is forcing clinicians to rethink their entire workflow, starting with diagnosis. In this episode of the BackTable Podcast, head and neck surgical oncologist Dr. Adam Luginbuhl is joined by colleagues Dr. Dylan Roden and Dr. Ravindra Uppaluri to discuss the implementation and implications of the Keynote-689 trial, which introduced neoadjuvant and adjuvant immunotherapy for locally advanced head and neck cancer.---SYNPOSISThe doctors discuss the trial details, FDA approval, and practical challenges of integrating this new paradigm into clinical practice. The conversation covers critical points such as the necessity of CPS score testing, timely drug administration, patient monitoring, and the importance of collaboration among multidisciplinary teams.---TIMESTAMPS00:00 - Introduction02:18 - Keynote-689 Trial Explained04:42 - Implementation Challenges and Strategies06:40 - Practical Considerations for CPS Testing13:59 - Case Studies and Real-World Applications30:48 - Future Directions and Final Thoughts---RESOURCESKeynote-689https://www.nejm.org/doi/full/10.1056/NEJMoa24154342004 Cisplatin Phase III Trialhttps://www.nejm.org/doi/full/10.1056/NEJMoa032646

Dr. Kelly Makielski and Dr. Jaime Modiano from the University of Minnesota join us on OsteoBites to discuss comparative extracellular vesicle (EV) biomarkers for osteosarcoma risk and prognosis.They are investigating extracellular vesicle (EV) transcriptomic profiles as minimally invasive biomarkers in canine and pediatric osteosarcoma in two ongoing studies. In the Canine Osteosarcoma Early Detection (COED) study, they are sequencing EV RNA from otherwise healthy dogs in breeds at elevated risk of osteosarcoma to identify gene signatures for the early detection and risk assessment of osteosarcoma. In parallel, they are conducting the KIDsCAN study, where we are sequencing EVs from pediatric osteosarcoma patients to identify prognostic signatures that could ultimately guide treatment intensity, aiming to minimize long-term therapy-associated morbidity without negatively impacting survival. Preliminary results from COED will be shared, along with how their comparative approach is helping to guide the KIDsCAN study.Kelly M. Makielski, DVM, DACVIM (SAIM) is an Assistant Professor of Small Animal Internal Medicine at the University of Minnesota College of Veterinary Medicine and Masonic Cancer Center. Her research focuses on extracellular vesicle (EV) biology and comparative oncology, using naturally occurring cancers in dogs to inform human cancer biology and treatment. She is the recipient of an NIH K01 investigating EV–based biomarkers for osteosarcoma prognosis in pediatric osteosarcoma, to guide personalized therapy and reduce treatment-related morbidity.Dr. Jaime Modiano holds the Alvin and June Perlman Endowed Chair of Animal Oncology and is director of the Animal Cancer Care and Research Program of the College of Veterinary Medicine and the Masonic Cancer Center, University of Minnesota. He completed his training through the Veterinary Medical Scientist Training Program (VMD, PhD) at the University of Pennsylvania, and he followed it with a residency in Clinical Pathology at Colorado State University and a post-doctoral fellowship at the National Jewish Center for Immunology and Respiratory Medicine. Before joining the University of Minnesota, he served on the faculties of Texas A&M University and the University of Colorado Health Sciences Center. Dr. Modiano has also worked in the private sector, as founder of several start-up companies, and as Director of Cancer Immunology and Immunotherapy for the Donald Monk Cancer Research Foundation. Through his research, Dr. Modiano seeks to understand how and why cancer happens and to develop strategies for improving the health and well-being of companion animals and humans alike.

Sally Wolf is back in the studio and this time we left cancer at the door. She turned 50, brought a 1993 Newsday valedictorian article as a prop, and sat down with me for a half hour of pure Gen X therapy. We dug into VHS tracking, Red Dawn paranoia, Michael J. Fox, Bette Midler, and how growing up with no helmets and playgrounds built over concrete somehow didn't kill us.We laughed about being Jewish kids in the suburbs, the crushes we had on thirty-year-olds playing teenagers, and what it means to hit 50 with your humor intact. This episode is part nostalgia trip, part roast of our own generation, and part meditation on the privilege of being alive long enough to look back at it all. If you ever watched Different Strokes “very special episodes” or had a Family Ties lunchbox, this one's for you.RELATED LINKSSally Wolf Official WebsiteSally Wolf on LinkedInSally Wolf on InstagramCosmopolitan Essay: “What It's Like to Have the ‘Good' Cancer”Oprah Daily: “Five Things I Wish Everyone Understood About My Metastatic Breast Cancer Diagnosis”Allure Breast Cancer Photo ShootTom Wilson's “Stop Asking Me the Question” SongFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship inquiries, email podcast@matthewzachary.com.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Dr. Bahar Mansoori explores how musculoskeletal complications from radiation therapy and immunotherapy can mimic metastatic disease and pose diagnostic challenges. She discusses key imaging patterns, pitfalls, and strategies radiologists can use to improve accuracy and patient care.   Musculoskeletal Complications of RadiationTherapy and Immunotherapy. Azhideh and Haseli et al. RadioGraphics 2025; 45(10):e250014. 

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Recent developments in these industries underscore a period of significant scientific progress, regulatory maneuvers, and strategic investments.One notable event was AstraZeneca and Daiichi Sankyo's success at the European Society for Medical Oncology Congress 2025. Their antibody-drug conjugate, Datroway, demonstrated superior efficacy compared to Gilead's Trodelvy in the first global head-to-head trial involving Trop2-targeted therapies. This reflects the increasing focus on antibody-drug conjugates as precision medicine tools that offer targeted treatment options with potentially improved outcomes over traditional chemotherapy.In a move highlighting the ongoing trend of bolstering domestic production capacities, Merck is making a substantial $3 billion investment in a small molecule drug plant in Virginia. This is part of a broader $70 billion commitment to expand manufacturing and R&D capabilities in the U.S. Such strategic investments are crucial for maintaining competitive advantage and ensuring drug availability while meeting rising demands and streamlining supply chains.Turning to regulatory updates, the FDA has approved Amgen and AstraZeneca's Tezspire for chronic rhinosinusitis with nasal polyps. This marks Tezspire's second indication, following its initial approval for severe asthma in 2021. The expanded approval showcases the drug's versatility and represents a strategic push to enhance its market presence against competitors like Dupixent.In oncology, Merck's Keytruda and Astellas/Pfizer's Padcev have made headlines with compelling results in muscle-invasive bladder cancer. The combination therapy reduced the risk of death by 50%, reinforcing Keytruda's position as a cornerstone immunotherapy across multiple cancer types. This result not only augments treatment options but also signifies the potential for combination regimens to enhance patient outcomes.Roche has expanded the indication of its aging oncology drug Gazyva to treat lupus nephritis, demonstrating strategic repurposing efforts to extend the lifecycle of existing therapies. While this expansion into autoimmune diseases comes late in Gazyva's lifecycle, it highlights a growing trend of capitalizing on established drugs for new therapeutic areas.AstraZeneca and Daiichi Sankyo's Enhertu showed robust efficacy in early breast cancer treatment, potentially reshaping therapeutic strategies by offering new hope for early intervention. Similarly, Novartis' Pluvicto demonstrated promise in slowing hormone-sensitive prostate cancer progression, underscoring the potential of radioligand therapies in oncology.However, not all developments have been positive. AstraZeneca faced setbacks when its Imfinzi and Lynparza combination failed to meet survival goals in ovarian cancer, underscoring the challenges inherent in oncology drug development and the stringent benchmarks set by regulatory authorities like the FDA.The industry is also witnessing significant advancements in next-generation ADCs, as evidenced by Tubulis' 59% response rate in early clinical trials, which has attracted substantial investor interest. Additionally, Grail's Galleri cancer blood test is progressing towards FDA review with enhanced performance data, potentially revolutionizing cancer screening and early detection practices.These scientific and regulatory milestones are complemented by strategic investments in bioconjugation technologies. Cohance Life Sciences' $10 million investment in NJ Bio to enhance GMP bioconjugation capabilities exemplifies this trend. Such investments are crucial for advancing ADC development, which remains a focal point for innovative cancer therapies.Overall, these developments reflect a dynamic phase for the pharmaceutical and biotech sectors characterized by signSupport the show

Commentary by Dr. Nicolas Palaskas & Dr. Keila Ostos-Mendoza.

Featuring an interview with Dr Aaron Lisberg, including the following topics: Efficacy and Safety of Datopotamab Deruxtecan (Dato-DXd) for Patients with Previously Treated EGFR-Mutated Advanced Non-Small Cell Lung Cancer (NSCLC): A Pooled Analysis of the TROPION-Lung01 and TROPION-Lung05 Trials (0:00) Ahn M-J et al. Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): A pooled analysis of TROPION-Lung01 and TROPION-Lung05. ESMO Asia 2024;Abstract LBA7 Ahn M-J et al. A pooled analysis of datopotamab deruxtecan in patients with EGFR-mutated NSCLC. J Thorac Oncol 2025;[Online ahead of print]. Abstract Sacituzumab Tirumotecan for Previously Treated Advanced EGFR-Mutated NSCLC: Results from the Randomized OptiTROP-Lung03 Study (7:08) Fang W et al. Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: Multicentre, open label, randomised controlled trial. BMJ 2025;389:e085680. Abstract Zhang L et al. Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC): Results from the randomized OptiTROP-Lung03 study. ASCO 2025;Abstract 8507. Combination of Dato-DXd and Immunotherapy as First-Line Therapy for Patients with Advanced NSCLC (13:12) Cuppens K et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) + durvalumab ± carboplatin in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohorts 2 and 4). ESMO Targeted Anticancer Therapies Congress 2025;Abstract 8O. Okamoto I et al. TROPION-Lung07: Phase III study of Dato-DXd + pembrolizumab ± platinum-based chemotherapy as 1L therapy for advanced non-small-cell lung cancer. Future Oncol 2024;20(37):2927-36. Abstract Levy BP et al. TROPION-Lung08: Phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. Future Oncol 2023;19(21):1461-72. Abstract Aggarwal C et al. AVANZAR: Phase III study of datopotamab deruxtecan (Dato-DXd) + durvalumab + carboplatin as 1L treatment of advanced/mNSCLC. World Conference on Lung Cancer (WCLC) 2023;Abstract P2.04-02. TROP2-Targeting Antibody-Drug Conjugates as Neoadjuvant and/or Adjuvant Therapy for Patients with Resectable NSCLC (19:08) A phase III, randomised, open-label, global study of adjuvant datopotamab deruxtecan (Dato-DXd) in combination with rilvegostomig or rilvegostomig monotherapy versus standard of care, following complete tumour resection, in participants with Stage I adenocarcinoma non-small cell lung cancer who are ctDNA-positive or have high-risk pathological features (TROPION-Lung12). NCT06564844 Cascone T et al. Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: The platform phase 2 NeoCOAST-2 trial. Nat Med 2025;31(8):2788-96. Abstract CME information and select publications

Dr. Nikki Maphis didn't just lose a grant. She lost a lifeline. An early-career Alzheimer's researcher driven by her grandmother's diagnosis, Nikki poured years into her work—only to watch it vanish when the NIH's MOSAIC program got axed overnight. Her application wasn't rejected. It was deleted. No feedback. No score. Just gone.In this episode, Oliver Bogler pulls back the curtain on what happens when politics and science collide and promising scientists get crushed in the crossfire. Nikki shares how she's fighting to stay in the field, teaching the next generation, and rewriting her grant for a world where even the word “diversity” can get you blacklisted. The conversation is raw, human, and maddening—a reminder that the real “war on science” doesn't happen in labs. It happens in inboxes.RELATED LINKS:• Dr. Nikki Maphis LinkedIn page• Dr. Nikki Maphis' page at the University of New Mexico• Vanguard News Group coverage• Nature article• PNAS: Contribution of NIH funding to new drug approvals 2010–2016FEEDBACK:Like this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship inquiries, visit outofpatients.com.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

GT Biopharma (NASDAQ: GTBP) is pioneering a new era in cancer treatment: one that replaces cutting, burning, and poisoning with precision, safety, and the power of the body's own immune system.In this interview, Executive Chairman & CEO Michael Breen and Consulting Senior Medical Director Dr. Jeffrey Miller discuss how GT Biopharma's TriKE® technology harnesses natural killer (NK) cells to target and destroy cancer cells, offering a more humane alternative to traditional therapies. They talk about the science behind their platform, the progress of ongoing Phase 1 clinical trials for blood cancer, upcoming FDA filings for solid tumors, and how next-generation nanobody and camelid technology is advancing efficacy and safety.Discover why GT Biopharma's platform represents one of the most promising innovations in immunotherapy and why investors are watching closely as key data milestones approach.Learn more about GT Biopharma: https://www.gtbiopharma.com/Watch the full YouTube interview here: https://youtu.be/he9i0aJQ2JMAnd follow us to stay updated: https://www.youtube.com/@GlobalOneMedia

Carla Tardiff has spent 17 years as the CEO of Family Reach, a nonprofit that shouldn't have to exist but absolutely does—because in America, cancer comes with a price tag your insurance doesn't cover.We talk about shame, fear, burnout, Wegmans, Syracuse, celebrity telethons, and the godforsaken reality of choosing between food and treatment. Carla's a lifer in this fight, holding the line between humanity and bureaucracy, between data and decency. She's also sharp as hell, deeply funny, and more purpose-driven than half of Congress on a good day.This episode is about the work no one wants to do, the stuff no one wants to say, and why staying angry might be the only way to stay sane.Come for the laughs. Stay for the rage. And find out why Family Reach is the only adult in the room.RELATED LINKSFamily ReachFinancial Resource CenterCarla on LinkedInMorgridge Foundation ProfileAuthority Magazine InterviewSyracuse University FeatureFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship inquiries, email podcast@matthewzachary.com.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

The advent of artificial light is obliterating women's moon-driven menstrual cycle rhythms; When the triple whammy of cataracts, glaucoma, and macular degeneration strikes; Why can systolic blood pressure spike erratically? Are wrist and finger wearables for blood pressure ready for prime time? Nearly half of drivers killed in crashes have THC in their blood; Drinking bottled water causes surge in plastic micro-particle intake; The common supplement that can supercharge cancer immunotherapy.

Dr. Hope Rugo and Dr. Giuseppe Curigliano discuss recent developments in the field of bispecific antibodies for hematologic and solid tumors, including strategies to optimize the design and delivery of the immunotherapy. TRANSCRIPT Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center. I am also the editor-in-chief of the Educational Book. Bispecific antibodies represent an innovative and advanced therapeutic platform in hematologic and solid tumors. And today, I am delighted to be joined by Dr. Giuseppe Curigliano to discuss the current landscape of bispecific antibodies and their potential to reshape the future of precision oncology. Dr. Curigliano was the last author of an ASCO Educational Book piece for 2025 titled, "Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances." Dr. Curigliano is a breast medical oncologist and the director of the Early Drug Development Division and chair of the Experimental Therapeutics Program at the European Institute of Oncology in Milan. He is also a full professor of medical oncology at the University of Milan. You can find our disclosures in the transcript of this episode. Dr. Curigliano, Giuseppe, welcome and thanks for being here. Dr. Giuseppe Curigliano: Thanks a lot for the invitation. Dr. Hope Rugo: Giuseppe, I would like to first ask you to provide some context for our listeners on how these novel therapeutics work. And then perhaps you could tell us about recent developments in the field of bispecific antibodies for oncology. We are at a time when antibody-drug conjugates (ADCs) are all the rage and, trying to improve on the targeting of specific antigens, proteins, receptors in the field of oncology is certainly a hot and emerging topic. Dr. Giuseppe Curigliano: So, thanks a lot. I believe really it was very challenging to try to summarize all the bispecific antibodies that are under development in multiple solid tumors. So, the first thing that I would like to highlight is the context and the mechanism of action of bispecific antibodies. Bispecific antibodies represent a groundbreaking advancement in cancer immunotherapy, because these engineered molecules have the unique ability to target and simultaneously bind to two distinct antigens. That is why we call them bispecific. So typically, one antigen is expressed on the tumor cell and the other one is expressed on the immune effectors, like T-cell or natural killer cells. So this dual targeting mechanism offers several key advantages over conventional monoclonal antibodies because you can target at the same time the tumor antigen, downregulating the pathway of proliferation, and you can activate the immune system. So the primary mechanism through which bispecific antibodies exert their therapeutic effects are: First, T-cell redirecting. I mean, many bispecific antibodies are designed to engage tumor-associated antigens like epidermal growth factor receptor, HER2, on the cancer cell and a costimulatory molecule on the surface of T-cell. A typical target antigen on T-cell is CD3. So what does it mean? That you activate the immune system, immune cells will reach the tumor bed, and you have a dual effect. One is downregulating cell proliferation, the other one is activation of the immune system. This is really important in hematological malignancies, where we have a lot of bispecifics already approved, like acute lymphoblastic leukemia or non-Hodgkin lymphoma.  The second, in fact, is the engagement of the tumor microenvironment. So, if you engage immune effector cells like NK cells or macrophages, usually the bispecific antibodies can exploit the immune system's ability to recognize and kill the immune cells, even if there is a lack of optimal antigen presentation.  And finally, the last mechanism of action, this may have a role in the future, maybe in the early cancer setting, is overcoming immune evasion. So bispecific antibodies can overcome some of the immune evasion mechanisms that we see in cancer. For example, bispecific antibodies can target immune checkpoint receptors, like PD-L1 and CTLA-4. Actually, there is a bispecific under development in breast cancer that has a dual targeting on vascular endothelial growth factor receptor and on PD-L1. So you have a dual effect at the same time. So, what is really important, as a comment, is we need to focus first on the optimal format of the bispecific, the optimal half-life, the stability, because of course even if they are very efficient in inducing a response, they may give also a lot of toxicities. So in clinical trials already, we have several bispecifics approved. In solid tumors, very few, specifically amivantamab for non-small cell lung cancer, but we have a pipeline of almost 40 to 50 bispecifics under development in multiple solid tumors, and some of them are in the context of prospective randomized trials. Dr. Hope Rugo: So this is really a fascinating area and it's really exciting to see the expansion of the different targets for bispecific antibodies. One area that has intrigued me also is that some of the bispecifics actually will target different parts of the same receptor or the same protein, but presumably those will be used as a different strategy. It's interesting because we have seen that, for example, in targeting HER2. Dr. Giuseppe Curigliano: Oh, yes, of course. You may consider some bispecifics like margetuximab, I suppose, in which you can target specifically two different epitopes of the same antigen. This is really an example of how a bispecific can potentially be more active and downregulating, let us say, a pathway, by targeting two different domains of a specific target antigen. This is an important point.  Of course, not all the bispecifics work this way, because some of the target antigen may dimerize, and so you have a family of target antigen; an example is epidermal growth factor receptor, in which you have HER1, HER2, HER3, and HER4. So some of them can inhibit the dimerization between one target antigen and the other one, in order to exert a more antiproliferative effect. But to be honest, the new generation of them are more targeting two different antigens, one on the tumor and one on the microenvironment, because according to the clinical data, this is a more efficient way to reduce proliferation and to activate the immune system. Dr. Hope Rugo: Really interesting, and I think it brings us to the next topic, which is really where bispecific antibodies have already shown success, and that is in hematologic malignancies where we have seen very interesting efficacy and these are being used in the clinic already. But the expansion of bispecific antibodies into solid tumors faces some key challenges. It's interesting because the challenges come in different shapes and forms. Tell us about some of those challenges and strategies to optimize bispecific antibody design, delivery, patient selection, and how we are going to use these agents in the right kind of clinical trials. Dr. Giuseppe Curigliano: This is really an excellent question because despite bispecific antibodies having shown a remarkable efficacy in hematological malignancies, their application in solid tumors may have some challenges. The first one is tumor heterogeneity. In hematological malignancy, you have a clear oncogene addiction. Let us say that 90% of the cells may express the same antigen. In solid tumors, it is not the same. Tumor heterogeneity is a typical characteristic of solid tumors, and you have high heterogeneity at the genetic, molecular, and phenotypic levels. So tumor cells can differ significantly from one another, even if within the same tumor. And this heterogeneity sometimes makes it difficult to identify a single target antigen that is universally expressed in an hematological malignancy. So furthermore, sometimes the antigen expressed on a tumor cell can be also present on the normal tissue. And so you may have a cross-targeting. So let's say, if you have a bispecific against epidermal growth factor receptor, this will target the tumor but will target also the skin with a lot of toxicity. The second challenge is the tumor microenvironment. The solid tumor microenvironment is really complex and often immunosuppressive. It is characterized by the presence of immunosuppressor cells like the T regulators, myeloid derived suppressor cells, and of course the extracellular matrix. All these factors hinder immune cell infiltration and also may reduce dramatically the effectiveness of bispecific antibodies. And as you know, there is also an hypoxic condition in the tumor. The other challenge is related to the poor tumor penetration. As you know also with antibody-drug conjugate, only 1 to 3% of the drug will arrive in the tumor bed. Unlike hematological malignancies where tumor cells are dispersed in the blood and easily accessible, the solid tumors have a lot of barriers, and so it means that tumor penetration can be very low. Finally, the vascularity also of the tumor can be different across solid tumors. That is why some bispecifics have a vascular endothelial growth factor receptor or vascular endothelial growth factor as a target. Of course, what do we have to do to overcome these challenges? First, we have to select the optimal antigen. So knowing very well the biology of cancer and the tumor-associated antigens can really select a subgroup of epitopes that are specifically overexpressed in cancer cells. And so we need to design bispecifics according to the tumor type. Second, optimize the antibody format. So there are numerous bispecific antibody formats. We can consider the dual variable domain immunoglobulin, we specified this in our paper. The single chain variable fragments, so FC variable fragments, and the diabodies that can enhance both binding affinity and stability. And finally, the last point, combination therapies. Because bispecific antibodies targeting immune checkpoint, we have many targeting PD-1 or PD-L1 or CTLA-4, combined eventually with other immune checkpoint inhibitors. And so you may have more immunostimulating effect. Dr. Hope Rugo: This is a fascinating field and it is certainly going to go far in the treatment of solid tumors. You know, I think there is some competition with what we have now for antibody-drug conjugates. Do you see that bispecifics will eventually become bispecific ADCs? Are we going to combine these bispecific antibodies with ADCs, with chemotherapy? What is the best combination strategy do you think looking forward? Dr. Giuseppe Curigliano: So, yes, we have a bispecific ADC. We have actually some bispecifics that are conjugated with a payload of chemotherapy. Some others are conjugated with immunoactivation agents like IL-2. One of the most effective strategies for enhancing bispecific activity is the combination therapy. So which type of combination can we do? First, bispecific antibodies plus checkpoint inhibitors. If you combine a bispecific with an immune checkpoint, like anti-PD-1, anti-PD-L1, or anti-CTLA-4, you have more activity because you have activation of T-cells, reduction of immunosuppressive effect, and of course, the capability of this bispecific to potentiate the activity of the immune checkpoint inhibitor. So, in my opinion, in a non-small cell lung cancer with an expression of PD-L1 more than 50%, if you give pembrolizumab plus a bispecific targeting PD-L1, you can really improve both response rate and median progression-free survival.  Another combination is chemotherapy plus bispecific antibodies. Combining chemotherapy with bispecific can enhance the cytotoxic effect because chemotherapy induces immunogenic cell death, and then you boost with a bispecific in order to activate the immune system. Bispecific and CAR T-cells, until now, we believe that these are in competition, but this is not correct. Because CAR T-cells are designed to deliver an activation of the immune system with the same lymphocytes engineered of the patients, with a long-term effect. So I really do not believe that bispecifics are in competition with CAR T-cells because when you have a complete remission induced by CAR T-cell, the effect of this complete remission can last for years. The activity of a bispecific is a little bit different. So there are some studies actually combining CAR T-cells with bispecifics. For example, bispecific antibodies can direct CAR T-cells in the tumor microenvironment, improving their specificity and enhancing their therapeutic effect.  And finally, monoclonal antibody plus bispecific is another next generation activity. Because if you use bispecific antibodies in combination with existing monoclonal antibodies like anti-HER2, you can potentially increase the immune response and enhance tumor cell targeting. In hematological malignancies, this has been already demonstrated and this approach has been particularly effective. Dr. Hope Rugo: That's just so fascinating, the whole idea that we have these monoclonal antibodies and now we are going to add them to bispecifics that we could maybe attach on different toxins to try and improve this, or even give them with different approaches. I suppose giving an ADC with a bispecific would sort of be similar to that idea of giving a monoclonal antibody with the bispecific. So it is certainly intriguing. We also will need to understand the toxicity and cost overall and how we are going to use these, the duration of treatment, the assessment of biomarkers. There are just so many different aspects that still need to be explored.  And then with that idea, can you look ahead five or ten years from now, and tell us how you think bispecific antibodies will shape our next generation cancer therapies, how they will be incorporated into precision oncology, and the new combinations and approaches as we move forward that will help us tailor treatment for patients both with solid tumors and hematologic malignancies? Are we going to be giving these in early-stage disease in solid tumors? So far, the studies are primarily focusing on the metastatic setting, but obviously one of the goals when we have successful treatments is to move them into the early stage setting as quickly as possible. Dr. Giuseppe Curigliano: Let us try to look ahead five years rather than ten years, to be more realistic. So, personally I believe some bispecifics can potentially replace current approaches in specifically T-cell selected population. As we gather more data from ongoing clinical trials and we adopt a deeper understanding of the tumor immuno microenvironment, of course we may have potentially new achievement. A few days ago, we heard that bispecifics in triple negative breast cancer targeting VEGF and PD-L1 demonstrated an improvement in median progression-free survival.  So, how to improve and to impact on clinical practice both in the metastatic and in the early breast cancer setting or solid tumor setting? First, personalized antigen selection. So we need to have the ability to tailor bispecific antibody therapy to the unique tumor profile of individual patients. So the more we understand the biology of cancers, the more we will be able to better target. Second, bispecific antibodies should be combined. I can see in the future a potential trial in which you combine a bispecific anti-PD-L1 and VEGF with immune checkpoint inhibitor selected also to the level of expression of PD-L1, because integration of antibody bispecific with a range of immunotherapies, and this cannot be only immune checkpoint inhibitors, but can be CAR T-cells, oncolytic viruses, also targeted therapy, will likely be a dominant theme in the coming years. This combination will be based on the specific molecular and immuno feature of the cancer of the patient.  Then we need an enhanced delivery system. This is really important because you know now we have a next generation antibody. An example are the bicyclic. So you use FC fragment that are very short, with a low molecular weight, and this short fragment can be bispecific, so can target at the same time a target antigen and improving the immune system. And so the development of this novel delivery system, including also nanoparticles or engineered viral vectors, can enhance the penetration in the tumor bed and the bioavailability of bispecific antibodies. Importantly, we need to reduce toxicity. Until now, bispecifics are very toxic. So the more we are efficient in delivering in the tumor bed, the more we will reduce the risk of toxicity. So it will be mandatory to reduce off-target effects and to minimize toxicity.  And finally, the expansion in new indication. So I really believe you raised an excellent point. We need to design studies in the neoadjuvant setting in order to better understand with multiple biopsies which is the effect on the tumor microenvironment and the tumor itself, and to generate hypotheses for potential trials or in the neoadjuvant setting or in those patients with residual disease.  So, in my opinion, as we refine design, optimize patient selection, and explore new combination, in the future we will have more opportunity to integrate bispecifics in the standard of care. Dr. Hope Rugo: I think it is particularly helpful to hear what we are going to be looking for as we move forward to try and improve efficacy and reduce toxicity. And the ability to engineer these new antibodies and to more specifically target the right proteins and immune effectors is going to be critical, of course, moving forward, as well as individualizing therapy based on a specific tumor biology.  Hearing your insights has been great, and it really has opened up a whole area of insight into the field of bispecifics, together with your excellent contribution to the ASCO Educational Book. Thank you so much for sharing your thoughts and background, as well as what we might see in the future on this podcast today. Dr. Giuseppe Curigliano: Thank you very much for the invitation and for this excellent interview. Dr. Hope Rugo: And thanks to our listeners for joining us today. You will find a link to the Ed Book article we discussed today in the transcript of this episode. It is also, of course, on the ASCO website, as well as on PubMed. Please join us again next month on By the Book for more insightful views on the key issues and innovations that are shaping modern oncology. 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  @hope.rugo  Dr. Giuseppe Curigliano @curijoey Follow ASCO on social media:       @ASCO on X (formerly Twitter)       ASCO on Bluesky      ASCO on Facebook       ASCO on LinkedIn       Disclosures:      Dr. Hope Rugo:   Honoraria: Mylan/Viatris, Chugai Pharma  Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer  Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  Dr. Giuseppe Curigliano: Leadership: European Society for Medical Oncology, European Society of Breast Cancer Specialists, ESMO Open, European Society for Medical Oncology Honoraria: Ellipses Pharma Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol-Myers Squibb, Samsung, AstraZeneca, Daiichi-Sankyo, Boerigher, GSK, Seattle Genetics, Guardant Health, Veracyte, Celcuity, Hengrui Therapeutics, Menarini, Merck, Exact Sciences, Blueprint Medicines, Gilead Sciences Speakers' Bureau: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, Seagen, Menarini, Gilead Sciences, Exact Sciences Research Funding: Merck Travel, Accommodations, Expenses: Roche/Genentech, Pfizer, Daiichi Sankyo, AstraZeneca      

JCO PO author Dr. Asaf Maoz at Dana-Farber Cancer Institute shares insights into article, “Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era.” Host Dr. Rafeh Naqash and Dr. Maoz discuss the causes of death in individuals with LS and the evolving role of immunotherapy. 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 Associate Professor Medicine, at the OU Health Stephenson Cancer Center. Today, I'm super thrilled to be joined by Dr. Asaf Maoz, Medical Oncologist at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and faculty at the Harvard Medical School, and also lead author on the JCO Precision Oncology article entitled "Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era." This publication will be a concurrent publication with an oral presentation at the annual CGA meeting. At the time of this recording, our guest's disclosures will be linked in the transcript. Asaf, I'm excited to welcome you on this podcast. Thank you for joining us today. Dr. Asaf Maoz: Thank you so much for highlighting our paper. Dr. Rafeh Naqash: Absolutely. And I was just talking to you that we met several years back when you were a trainee, and it looks like you've worked a lot in this field now, and it's very exciting to see that you consider JCOPO as a relevant home for some of your work. And the topic that you have published on is of significant interest to trainees from a precision medicine standpoint, to oncologists in general, covers a lot of aspects of immunotherapy. So, I'm really excited to talk to you about all of this. Dr. Asaf Maoz: Me too, me too. And yeah, I think JCOPO has great content in the area of cancer genetics and has done a lot to disseminate the knowledge in that area. Dr. Rafeh Naqash: Wonderful. So, let's get started and start off, given that we have hosts of different kinds of individuals who listen to this podcast, especially when driving from home to work or back, for the sake of making everything simple, can we start by asking you what is Lynch syndrome? How is it diagnosed? What are some of the main things to consider when you're trying to talk an individual where you suspect Lynch syndrome? Dr. Asaf Maoz: Lynch syndrome is an inherited predisposition to cancer, and it is common. So, we used to think that, or there's a general notion in the medical community that it is a rare condition, but we actually know now from multiple studies, including studies that look at the general population and do genetic testing regardless of any clinical phenotype, that Lynch syndrome is found in about 1 in 300 people in the general population. If you think about it in the United States, that means that there are over a million people living with Lynch syndrome in the United States. Unfortunately, most individuals with Lynch syndrome don't know they have Lynch syndrome at the current time, and that's where a lot of the efforts in the community are being made to help detect more individuals who have Lynch syndrome. Lynch syndrome is caused by pathogenic germline variants in mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, or as a result of pathogenic variants in EPCAM that cause silencing of the MSH2 gene. Dr. Rafeh Naqash: Excellent. Thank you for that explanation. Now, one of the other things I also realized, similar to BRCA germline mutations, where you require a second hit for individuals with Lynch syndrome to have mismatch repair deficient cancers, you also require a second hit to have that second hit result in an MSI-high cancer. Could you help us understand the difference of these two concepts where generally Lynch syndrome is thought of to be cancers that are mismatch repair deficient, but that's not necessarily true for all cases as we see in your paper. Can you tease this out for us a little bit more? Dr. Asaf Maoz: Of course, of course. So, the germline defect is in one of the mismatch repair genes, and these genes are responsible for DNA mismatch repair, as their name implies. Now, in a normal cell, we think that one working copy is generally enough to maintain the mismatch repair machinery intact. What happens in tumors, as you alluded to, is that there is a second hit in the same mismatch repair gene that has the pathogenic germline variant, and that causes the mismatch repair machinery not to work anymore. And so what happens is that there is formation of mutations in the cancer cell that are not present in other cells in the body. And we know that there are specific types of mutations that are associated with defects in mismatch repair mechanisms, and those are associated a lot of times with frameshift mutations. And we have termed them ‘microsatellites'. So there are areas in the genome that have repeats, for example, you know, if you have AAAA or GAGA, and those areas are particularly susceptible to mutations when the mismatch repair machinery is not working. And so we can measure that with DNA microsatellite instability testing. But we can also get a sense of whether the mismatch repair machinery is functioning by looking at protein expression on the surface of cancer cells and by doing immunohistochemistry. More recently, we're also able to infer whether the mismatch repair machinery is working by doing next-generation sequencing and looking at many, many microsatellites and whether they have this DNA instability in the microsatellites. Dr. Rafeh Naqash: Excellent explanation. As a segue to what you just mentioned, and this reminds me of some work that one of my good friends, collaborators, Amin Nassar, whom you also know, I believe, had done a year and a half back, was published in Cancer Cell as a brief report, I believe, where the concept was that when you look at these mismatch repair deficient cancers, there is a difference between NGS testing, IHC testing, and maybe to some extent, PCR testing, where you can have discordances. Have you seen that in your clinical experience? What are some of your thoughts there? And if a trainee were to ask, what would be the gold standard to test individuals where you suspect mismatch repair deficient-related Lynch syndrome cancers? How would you test those individuals? Dr. Asaf Maoz: We do sometimes see discordance, you know, from large series, the concordance rate is very high, and in most series it's over 95%. And so from a practical perspective, if we're thinking about the recommendation to screen all colorectal cancer and all endometrial cancer for mismatch repair deficiency, I think either PCR-based testing or immunohistochemistry is acceptable because the concordance rate is very high. There are rare cases where it is not concordant, doing multiple of the tests makes sense at that time. If you think about the difference between the tests, the immunohistochemistry looks at protein expression, which is a surrogate for whether there is mismatch repair deficiency or not, right? Because ultimately, the mismatch repair deficiency is manifested in the mutations. So if the PCR does not show microsatellite instability and now NGS does not show microsatellite instability, the IHC may be a false positive. At the end of the day, the functional analysis of whether there are actually unstable microsatellites either by PCR or by NGS is what I would consider more informative. But IHC again is an excellent test and concordant with those results in over 95% of cases. Now there is also an issue of sampling. It's possible that there's heterogeneity within the tumor. We published a case in JCOPO about heterogeneity of the mismatch repair status, and that was both by immunohistochemistry, but also by PCR. So there are some caveats and interpreting these tests does require some expertise, and I'm always happy to chat with trainees or whoever has an interesting or challenging case. Dr. Rafeh Naqash: Thanks again for that very easy to understand explanation. Now going to management strategies, could you elaborate a little bit upon the neo-adjuvant data currently, or the metastatic data which I think more people are familiar with for immunotherapy in individuals with MSI-high cancers? Dr. Asaf Maoz: Yeah, that's an excellent question and obviously a very broad topic. Individuals with Lynch syndrome typically develop tumors that are mismatch repair deficient or microsatellite unstable. And we have seen over the last 15 years or so that these tumors, because they have a lot of mutations and because these mutations are very immunogenic, we have seen that they respond very well to immunotherapy. And this has been shown across disease sites and has been shown across disease settings. And for that reason, immunotherapy was approved for MSI-high or mismatch repair deficient cancer regardless of the anatomic site. It was the first tissue-agnostic approval by the FDA in 2017. And so there are exciting studies both in the metastatic setting where we see individuals who respond to immunotherapy for many years, and one could wonder whether their cancer is going to come back or not. And also in the earlier setting, for example, the Cercek et al. study in the New England Journal from Sloan Kettering, where they showed that neoadjuvant immunotherapy can cause durable responses for rectal cancer that is mismatch repair deficient. And in that series, the patients did not require surgery or radiation, which is standard of care for rectal cancer otherwise. And there's also exciting data in the adjuvant space, as was presented in ASCO by Dr. Sinicrope, the ATOMIC study, and many more efforts to bring immunotherapy into the treatment landscape for individuals with MSI-high cancer, including individuals with Lynch syndrome. Dr. Rafeh Naqash: A lot of activity, especially in the neo-adjuvant and adjuvant space over the last two years or so. Now going to the actual reason why we are here is your study. Could you tell us why you looked at this idea of patients who had Lynch syndrome and died, and the reasons for their death? What was the thought that triggered this project? Dr. Asaf Maoz: As we were talking about, we now know that immunotherapy really has changed the treatment landscape for individuals with Lynch syndrome, and that most cancers that individuals with Lynch syndrome do have this mismatch repair deficiency. But we also know that individuals with Lynch syndrome can develop tumors that do not have mismatch repair deficiency, and we call them mismatch repair proficient or microsatellite stable. And there was a series from Memorial Sloan Kettering showing that in colorectal cancer, about 10% of the tumors that individuals with Lynch syndrome developed did not have mismatch repair deficiency. In addition to that, we anecdotally saw that some of our patients with Lynch syndrome died of causes that were not mismatch repair deficient tumors. We wanted to see how that has changed since immunotherapy was approved in a tissue-agnostic manner, meaning that we could look at this regardless of where the cancer started, because we would anticipate that if the tumor was mismatch repair deficient, the patient would be able to access immunotherapy as standard of care. Dr. Rafeh Naqash: Thank you. And then you looked at different aspects of correlations with regards to individuals that had an MSI-high cancer with Lynch syndrome or an MSS cancer with Lynch syndrome. Could you elaborate on some of the important findings that you identified as well as some of the unusual findings that perhaps we did not know about, even though the sample size is limited, but what were some of the unique things that you did identify through this project? Dr. Asaf Maoz: The first question was what cause is leading to death in individuals with Lynch syndrome? And we had 54 patients that we identified that had died since the approval of immunotherapy in 2017, 44 of which died of cancer-related causes. And when we looked at cancer-related causes of death, we wanted to know how many of those were due to mismatch repair deficient tumors versus mismatch repair proficient tumors or MS-stable tumors. And we found, somewhat surprisingly, that 43% of patients in our cohort actually died of tumors that were microsatellite stable or mismatch repair proficient, meaning of tumors that are not typically associated with Lynch syndrome. This is not entirely surprising as a cause of death because we know that immunotherapy does not typically work for tumors that are microsatellite stable. And so in the metastatic setting, there are much less cases of durable remissions with treatment. But it was helpful to have that figure as an important benchmark. There are previous studies about causes of death in Lynch syndrome, and particularly from the Prospective Lynch Syndrome Database in Europe. Those have provided really important information about cause of death by cancer site, but they typically don't have mismatch repair status and are more difficult to interpret in that regard. They also don't include a large number of individuals who have PMS2 Lynch syndrome, which is the most common, but least penetrant form of Lynch syndrome. Dr. Rafeh Naqash: As far as the subtype of pathogenic germline variants is concerned, did you notice anything unusual? And I've always had this question, and you may know more about this data, is: In the bigger context of immunotherapy, does the type of the pathogenic germline variant for Lynch syndrome associated MSI-high cancers, does that impact or have an association with the kind of outcomes, how soon a cancer progresses or how many exceptional responders perhaps with MSI-high cancers actually have a certain specific pathogenic germline variant? Dr. Asaf Maoz: That's an excellent question, and certainly we need more data in that space. We know that the type of germline mutation, or the gene in which there is a germline pathogenic variant, determines to a large degree the cancer risk, right? So we know that individuals who have germline pathogenic variants in MLH1 or MSH2 have a much higher colorectal cancer risk than, for example, PMS2. We know that for PMS2, the risks are more limited to colorectal and endometrial, and may be lower risk of other cancers. We also know that, you know, the spectrum of disease may change based on the pathogenic germline variants. For example, individuals who have MSH2 associated Lynch syndrome have more risk of additional cancers in other organs like the urinary tract and other less common Lynch-associated tumors. The question about response to therapy is one where we have much less information. There are studies that are trying to assess this, but I don't think the answer is there yet. Some of the non-clinical data looks at how many mutations there are based on the pathogenic variant and what the nature of those mutations are, whether they're more frameshift or others. But I think we still need more clinical data to understand whether the response to immunotherapy differs. It's also complicated by the fact that the immunotherapy landscape is changing, especially in the metastatic setting, now with the approval of combination ipilimumab and nivolumab for first-line treatment of colorectal cancer that is microsatellite unstable. But in our study, we did find that, as you would expect, there is an enrichment in MS-stable cancers among those with PMS2 Lynch syndrome. Again, our denominator is those who died, right? So this is not the best way to look at the question whether this is overall true, that is more addressed by the study that Sloan Kettering published. But we do see, as we would anticipate, that there are more microsatellite stable cancers among those with PMS2 Lynch syndrome that died. Dr. Rafeh Naqash: A lot to uncover there for sure. This study and perhaps some of the other work that you're doing is slowly advancing our understanding of some of these concepts. So I'd like to shift gears to a couple of provocative questions that I generally like to ask. The first is, in your opinion, and you may or may not have data to back this up, which is okay, and that's why we're having a conversation about it. In your opinion, do you think the type or the quality of the neoantigen is different based on the pathogenic germline variant and a Lynch syndrome associated MSI-high cancer? Dr. Asaf Maoz: I think there are some data out there that, you know, I can't cite off the top of my mind, but there are some data out there that suggest that that may be the case. I think the key question is the quality, right? I think that whether these differences that are found on a molecular level also translate to a clinical difference in response is something that is unknown at this moment. Some people hypothesize that if the tumor has less neoantigens, there's less of a response to immunotherapy. But I think we really need to be careful before making those assertions on a clinical level. I do think it's a really important question that needs to be answered, among others because, you know, in the colorectal space, for example, where we have both the option of doing ipilimumab with nivolumab and the option of doing pembrolizumab, we don't really know which patients need the CTLA-4 blockade versus which patients can receive PD-1 blockade alone and avoid the potential excess toxicity of the CTLA-4 blockade. There are a lot of interesting questions there that still need to be answered. And of course, individuals with Lynch syndrome are just a fraction of those individuals who have MSI-high cancer. So there's also the question about whether non-Lynch syndrome associated MSI-high cancer responds differently to immunotherapy than Lynch syndrome associated MSI-high cancer. A lot of very interesting questions in the field for sure. Dr. Rafeh Naqash: Absolutely. My second question is more about trying to understand the role of ctDNA, MRD monitoring in individuals with Lynch syndrome. If somebody has a germline, you know, Lynch syndrome MSI-high cancer, when you do a tumor-informed ctDNA assessment, what do you capture generally there? Because, and this question stems from a discussion I've had with somebody regarding EGFR lung cancer, since I treat individuals with lung cancer, and the concept generally is that even if the tissue showed EGFR, but for MRD monitoring, when you do a barcoded sequence of different tumor specific mutations, it's not actually the EGFR that they track in the blood when they do ctDNA assessment. But from a Lynch syndrome standpoint, if you have a germline, right, which is the first hit, and then you have the somatic in the tumor, which is the second hit, are you aware or have you tried to look into this where what is exactly being followed if one had to follow MRD in a Lynch syndrome MSI-high colorectal cancer? Dr. Asaf Maoz: I think a lot of the MRD assays are proprietary, and so we don't receive information about what the mutations that are being tracked are. In general, the idea is to track mutations that we would not expect to disappear as part of resistant mechanisms. We want these to be truncal mutations. We want these to be mutations in which resistance is not expected to result in reversion mutations. But what specifically is being tracked is something that I don't know because these assays, the tumor-informed ones, are proprietary, and we don't get the results regarding specific mutations. When it's circulating tumor DNA that is not necessarily tumor-informed, we do get those results, but that is less so about the specific selection of mutations. Dr. Rafeh Naqash: Thank you for clarifying that question to some extent, of course, as you said, we don't know a lot, and we don't know what we don't know. That's the most important thing that I've learned in the process of understanding precision medicine and genomics, and it's a very fast-paced evolving field. Last question related to your project, what is the next step? Are you planning any next steps as a bigger multicenter study or validation of some sort? Dr. Asaf Maoz: There are two big questions that this study raises. One, is this true across multiple other sites, right? Because this is a single center study, and we really need additional centers to look at their data and validate whether they are also seeing that a substantial portion of deaths in individuals with Lynch syndrome are attributable to mismatch repair proficient cancer. The other question is whether we can look at specifically MSI-high cancer versus MS-stable cancer and understand what the mortality rate for each of those are. From a clinical perspective, it's important to counsel individuals with Lynch syndrome about general cancer screening outside of mismatch repair deficient tumors and to understand that there is also a risk of mismatch repair proficient tumors and that treatment for those tumors would be different. There's a lot of work to be done in the future. Another major area of need is to see whether tumors that are microsatellite stable can be sensitized to immunotherapy, and that is beyond the Lynch syndrome field, but that is something that certainly would benefit these individuals with Lynch syndrome who develop mismatch repair proficient cancer. Dr. Rafeh Naqash: That's very interesting to hear, and we'll look forward to seeing some of those developments shape in the next few years. Now, I'd like to spend a minute, minute and a half on you specifically as a researcher, clinician, scientist. Could you briefly highlight - because I remember meeting you several years back as a trainee, with your interest in genomics, computational research - could you briefly tell us what led you to hereditary cancer syndromes based on your research and work? What are some of the things that you learned along the way that other early career investigators can perhaps take lessons from? Dr. Asaf Maoz: Big questions there, thanks for asking. I got interested in the field of hereditary cancer syndromes when I came to the United States and started doing lab research in Stephen Gruber's lab at the time at USC. He's now at City of Hope. And my interest was originally looking at immunotherapy and immunology, but I went to the case conferences where we were learning about individuals with hereditary cancer, and those were kind of earlier days where we were still trying to figure out how to test and what the implications for these individuals would be. And through fellowship, I was also very interested in that, and I did my senior fellowship years with Dr. Yurgelun here at Dana-Farber, who is the director of the Lynch Syndrome Center. And I I think it's the combination between being able to treat individuals based on precision medicine and what the germline mutation is, but also the ability to prevent cancer and to develop strategies to intercept cancer early that is really appealing to me in this field. It's also a great field to be in because it's a small field. If you come to the CGA-IGC meeting, you'll be able to interact with everyone. Everyone is super collaborative, super nice, and I really recommend it to trainees. The CGA-IGC annual meeting is really a great opportunity to learn more and experience some of the advancement specifically in the GI hereditary space. Lessons for trainees. I think there are a lot of lessons that I could think about, but I think finding strong and supportive mentors is one of the things that has helped me most. I think that just having close relationship with your mentor, having frequent discussions and honest discussions about what is feasible, what is going to make a difference for your patients and your research and what you want to focus on is really important. And so I think if I had to choose one thing, I would say choose a mentor that you trust, that you feel you have a good relationship with, and that has the availability to support you. Dr. Rafeh Naqash: Thank you so much for those insightful comments, and thank you for sharing with us your journey, your project, and some of your interesting thoughts on this concept of hereditary cancers. Hopefully, we'll see more of this work being published in JCOPO through your lab or work from others. Dr. Asaf Maoz: Thank you so much. I appreciate the opportunity to be here. Dr. Rafeh Naqash: 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.

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Jennifer J. Brown is a scientist, a writer, and a mother who never got the luxury of separating those roles. Her memoir When the Baby Is Not OK: Hopes & Genes is a punch to the gut of polite society and a medical system that expects parents to smile through trauma. She wrote it because she had to. Because the people who gave her the diagnosis didn't give her the truth. Because a Harvard-educated geneticist with two daughters born with PKU still couldn't get a straight answer from the very system she trained in.We sat down in the studio to talk about the unbearable loneliness of rare disease parenting, the disconnect between medical knowledge and human connection, and what it means to weaponize science against silence. She talks about bias in the NICU, the failure of healthcare communication, and why “resilience” is a lazy word. Her daughters are grown now. One's a playwright. One's an artist. And Jennifer is still raising hell.This is a conversation about control, trauma, survival, and rewriting the script when the world hands you someone else's lines.Bring tissues. Then bring receipts.RELATED LINKS• When the Baby Is Not OK (Book)• Jennifer's Website• Jennifer on LinkedInFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship inquiries, visit outofpatients.show.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

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Dr. Rahul Aggarwal presents emerging treatments for advanced prostate cancer, highlighting rapid advances in drug development. He outlines therapies targeting cancer cell surface proteins beyond PSMA, including CD46, B7-H3, and DLL3, and explains how antibody-drug conjugates deliver potent chemotherapy directly to tumors. He also discusses bispecific T-cell engagers designed to trigger immune attacks on cancer cells, including promising results from agents like Talquetamab. Aggarwal explores new isotopes such as actinium-225 for radioligand therapy, which may offer stronger and more durable responses than current treatments. He emphasizes continued innovation in targeting the androgen receptor, with drugs that degrade the receptor or block androgen production more effectively than existing therapies. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 40813]

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/EDR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Maximizing the Potential and Expanding the Impact of Immunotherapy in Advanced NSCLC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through an independent educational grant from Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.

This episode of Standard Deviation features Oliver Bogler in conversation with Dr Na Zhao, a cancer biologist caught in the crossfire of science, politics, and survival. Na's life reads like a brutal lab experiment in persistence.She grew up in China, lost her mother and aunt to breast cancer before she turned twelve, then came to the United States to chase science as both an immigrant and a survivor's daughter. She worked two decades to reach the brink of independence as a cancer researcher, only to watch offers and grants vanish in the political chaos of 2025.Oliver brings her story into sharp focus, tracing the impossible climb toward a tenure-track position and the human cost of a system that pulls the ladder up just as people like Na reach for it. This conversation pulls back the curtain on the NIH funding crisis, the toll on early-career scientists, and what happens when personal tragedy fuels professional ambition.Listeners will walk away with a raw sense of how fragile the future of cancer research really is, and why people like Na refuse to stop climbing.RELATED LINKSDr Zhao at Baylor College of MedicineDr Zhao on LinkedInDr Zhao's Science articleIndirect Costs explained by US CongressFEEDBACKLike this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship inquiries, email podcast@matthewzachary.comSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

What if cancer treatment could harness the body's own immune system instead of relying on surgery, radiation, or chemotherapy? GT Biopharma (NASDAQ: GTBP) is developing its TriKE® platform, a novel NK cell engager designed to activate natural killer cells to seek out and destroy cancer.In this interview, Executive Chairman & CEO Michael Breen discusses the company's origins, the science behind its technology, and its progress in clinical trials for acute myeloid leukemia. He also outlines GT Biopharma's plans to expand into solid tumors and autoimmune diseases, highlighting the commercial potential and challenges ahead. Watch the full interview to learn how the company is advancing immunotherapy in a new direction.Learn more about GT Biopharma: https://www.gtbiopharma.com/ Watch the full YouTube interview here: https://youtu.be/Z9tNa4JTELwAnd follow us to stay updated: https://www.youtube.com/@GlobalOneMedia?sub_confirmation=1

Recently the Endocrine Society held its 12th annual Type 1 Diabetes Fellows Series program, which combines comprehensive education on type 1 diabetes with career development opportunities to build knowledge, practical skills, and a lasting network of colleagues. For this episode, host Aaron Lohr talks with Desmond Schatz, MD, medical director of the Diabetes Institute and director of the Clinical Research Center at the University of Florida. Dr. Schatz gave a talk at the fellows series program titled, “Immunotherapies for Type 1 Diabetes: Need for Early Detection and Screening.” This year’s fellows series program and this episode were made possible by the support of Abbott Diabetes Care, CeQur Corp., Dexcom Inc., Insulet Corp., Breakthrough T1D (formerly the Juvenile Diabetes Research Foundation), Lilly USA, Mankind Pharma Limited, Medtronic Inc., Novo Nordisk Inc., and Vertex Pharmaceuticals Inc. Show notes are available at https://www.endocrine.org/podcast/enp103 — for helpful links or to hear more podcast episodes, visit https://www.endocrine.org/podcast

Katie Henry has seen some things. From nonprofit bootstraps to Big Pharma boardrooms, she's been inside the machine—and still believes we can fix it. We go deep on her winding road from folding sweaters at J.Crew to launching a vibrator-based advocacy campaign that accidentally changed the sexual health narrative in breast cancer.Katie doesn't pull punches. She's a born problem solver with zero tolerance for pink fluff and performative empathy. We talk survivor semantics, band camp trauma, nonprofit burnout, and why “Didi” is the grandparent alter ego you never saw coming.She's Murphy Brown with a marimba. Veronica Sawyer in pharma. Carla Tortelli with an oncology Rolodex. And she still calls herself a learner.This is one of the most honest, hilarious, and refreshingly real conversations I've had. Period.RELATED LINKS:Katie Henry on LinkedInKatie Henry on ResearchGateLiving Beyond Breast CancerNational Breast Cancer CoalitionFEEDBACK:Like this episode? Rate and review Out of Patients on your favorite podcast platform. For guest suggestions or sponsorship inquiries, email podcast@matthewzachary.com.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Lung cancer is one of the world's biggest killers. Today, we explore why, and how medical research into this disease is seeing the development of better diagnostic tools, cancer treatments and even a vaccine to prevent tumours from taking hold in the first place... Like this podcast? Please help us by supporting the Naked Scientists