Podcasts about ngs

Just back from IDWeek 2025 in Atlanta, Luis shares the sessions and posters that defined this year's meeting — from next-generation sequencing and diagnostic stewardship to AI in the microbiology lab and new antimicrobials on the horizon. Tune in for insights on: NGS test utilization and stewardship New β-lactamase inhibitors like nacubactam  AI's growing role in clinical microbiology Tedizolid and the importance of optimizing existing agents

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare blood cancer that primarily affects older adults. One of the key challenges in diagnosing and treating BPDCN is that it closely resembles other forms of leukemia in both appearance and behavior. This overlap often leads to delays or uncertainty in diagnosis, especially since currently there is no single, reliable marker that clearly distinguishes BPDCN from related diseases. To address this issue, researchers from the City of Hope Comprehensive Cancer Center investigated the genetic profile of BPDCN. Their study, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience,” was published in Oncotarget (Volume 16). Full blog - https://www.oncotarget.org/2025/10/22/genetic-study-identifies-potential-diagnostic-marker-for-rare-blood-cancer-bpdcn/ Paper DOI - https://doi.org/10.18632/oncotarget.28742 Correspondence to - Michelle Afkhami - mafkhami@coh.org Abstract video - https://www.youtube.com/watch?v=wUjr3uU3onI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28742 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50 To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

En esta cápsula de ESMO 2025 EXPRESS, el Dr. Sergio Vázquez Estévez, oncólogo médico adscrito al Hospital Universitario Lucus Augusti en Lugo, España, nos habla sobre los principales avances presentados en tumores genitourinarios.El experto comenta lo siguiente:Durante el Congreso Anual de la Sociedad Europea de Oncología Médica 2025, se presentaron resultados que redefinen el manejo de los tumores genitourinarios, destacando avances en cáncer de vejiga, renal y de próstata.En cáncer de vejiga no músculo infiltrante, el estudio POTOMAC (fase III) mostró que durvalumab intravenoso más BCG intravesical mejora la supervivencia libre de enfermedad frente a BCG solo. Sin embargo, se debate si este beneficio justifica la toxicidad de grado 3 (~20%) y si la supervivencia libre de cistectomía debería considerarse el objetivo clínico más relevante.En cáncer de vejiga músculo infiltrante, el ensayo EV-303 fue uno de los más destacados del congreso: la combinación enfortumab vedotin + pembrolizumab en el contexto perioperatorio superó al tratamiento estándar (cistectomía radical más quimioterapia con cisplatino) con mejoras significativas en supervivencia libre de enfermedad, supervivencia global y tasa de respuestas patológicas completas (~57%). Estos resultados abren la posibilidad de estrategias futuras de preservación vesical basadas en ctDNA y resonancia magnética.En el escenario metastásico, un estudio fase III en pacientes con expresión alta de HER2 (1–3 +) demostró que la combinación de un anticuerpo conjugado anti-HER2 (sistema B2C1) con el anti-PD-1 doriplimab mejora la supervivencia libre de enfermedad y global frente al doblete con platino. No obstante, la tasa de respuestas completas (

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.

In this episode of the Oncology Brothers podcast, we are joined by Dr. Omid Hamid, a melanoma specialist from Cedars-Sinai, to explore the current treatment landscape of cutaneous melanoma. We covered a wide range of topics, including: •⁠  ⁠The standard of care for early-stage melanoma, including wide local excision and sentinel lymph node evaluation. •⁠  ⁠The role of adjuvant immunotherapy and BRAF/MEK inhibitors for high-risk patients. •⁠  ⁠Insights into neoadjuvant treatment options for resectable disease, including recent trial data from NADINA and SWOG S1808. •⁠  ⁠The importance of next-generation sequencing (NGS) and circulating tumor DNA (ctDNA) in treatment planning and monitoring. •⁠  ⁠The evolving treatment paradigm for metastatic melanoma, including the use of dual checkpoint inhibitors and BRAF/MEK inhibitors. Join us as we discuss the latest advancements in melanoma treatment and the critical role of patient education and shared decision-making in oncology care. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for more episodes on treatment algorithms, new FDA approvals, and conference highlights! #Melanoma #Immunotherapy #BRAF #ctDNA #Neoadjuvant #OncologyBrothers

JCO PO author Dr. Alison M. Schram at Memorial Sloan Kettering Cancer Center shares insights into her JCO PO article, “Retrospective Analysis of BRCA-Altered Uterine Sarcoma Treated With Poly(ADP-ribose) Polymerase Inhibitors.” Host Dr. Rafeh Naqash and Dr. Schram discuss relevant genomic and clinical features of patients with BRCA-altered uterine sarcoma and the efficacy of PARPis in this population. 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 JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and associate professor at the OU Health Stephenson Cancer Center. Today, we are excited to be joined by Dr. Alison Schram, Associate Attending Physician and Section Head of Oral Therapeutics with Early Drug Development and Gynecologic Medical Oncology Services at the Memorial Sloan Kettering Cancer Center, and the senior author of the JCO Precision Oncology article titled, "Retrospective Analysis of BRCA-Altered Uterine Sarcoma Treated With Poly(ADP-ribose) Polymerase Inhibitors." At the time of this recording, our guest's disclosures will be linked in the transcript. Dr. Schram, thank you for joining us today. I am excited to be discussing this very interesting, unique topic based on what you published in JCO PO. Dr. Alison Schram: Thank you for having me. Dr. Rafeh Naqash: What we like to do for these podcasts is try to make them scientifically interesting but at the same time, keep them at a level where our trainees and other community oncology professionals understand the implications of what you've published. So I'd like to start by asking you, what is leiomyosarcoma for those of us who don't necessarily know a lot about leiomyosarcoma, and what are some of the treatment options for these uterine sarcomas? Dr. Alison Schram: Uterine leiomyosarcoma is a rare subtype of uterine cancer, and it represents about 1% of all female cancers in the reproductive tract. This is a rare malignancy that arises from the myometrial lining of the uterus, and it is generally pretty aggressive. In terms of the standard therapy, the standard therapy for uterine leiomyosarcoma includes chemotherapy, generally combination chemotherapy, but despite a few regimens that tend to be effective, the duration of effectiveness is relatively short-lived, and patients with advanced uterine leiomyosarcoma eventually progress and require additional therapy. I will say that localized uterine leiomyosarcoma can be treated with surgery as well. Dr. Rafeh Naqash: Thank you for that description. Now, there are two aspects to what you published. One is the sarcoma aspect, the leiomyosarcoma, and the second is the BRCA mutation. Since we are a precision medicine journal, although we've discussed BRCA a couple of times before, but again, for the sake of our listeners, could you highlight some of the aspects of BRCA and PARP sensitivity for us? Dr. Alison Schram: Yes. So BRCA is a gene that's important for DNA repair, and BRCA mutations can be either inherited as a germline mutation, so one of your parents likely had a BRCA mutation and you inherited one copy. In patients who have an inherited BRCA mutation, the normal cells tend to have one abnormal copy of BRCA, but if a second copy in the cell becomes altered, then that develops into cancer. And so these patients are at increased risk of developing cancers. Specifically, they are at an increased risk of developing ovarian cancer, breast cancer, prostate cancer, pancreatic cancer, and a few others. These cancers are considered BRCA-associated tumors. Alternatively, some patients, more rarely, can develop BRCA-altered cancers completely sporadically. So it's a mutation that happens in the tumor itself, and that can lead to impaired DNA repair and promote cancer progression. And those patients are not, they don't have any inherited risk, but just a random event caused a BRCA mutation in the tumor. The reason this is important is because, in addition to it being potentially important for family members, there are certain treatments that are more effective in BRCA-altered cancers. And the main example is PARP inhibitors, which are small molecule inhibitors that inhibit the PARP enzyme, and there is what we call synthetic lethality. So PARP is important for DNA repair, for single-stranded DNA repair, BRCA is important for double-stranded DNA repair, and in a patient that has a cancer that has a BRCA mutation, that cancer becomes more reliant on single-stranded DNA repair. And if you inhibit it with a PARP inhibitor, the cancer cells are unable to repair DNA, and the cells die. So we call that synthetic lethality. PARP inhibitors are FDA approved in several diseases, predominantly the BRCA-associated diseases I mentioned: breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer. Dr. Rafeh Naqash: That was very beautifully explained. Honestly, I've heard many people explain BRCA before, but you kind of put it in a very simple, easy to understand format. You mentioned this earlier describing germline or hereditary BRCA and somatic BRCA. And from what I gather, you had a predominant population of somatic BRCA, but a couple of germline BRCA as well in your patient population, which we'll go into details as we understand the study. You mentioned the second hit on the germline BRCA that is required for the other copy of the gene to be altered. In your clinical experience, have you seen outside of the study that you published, a difference in the sensitivity of PARP for germline BRCA versus a somatic BRCA that has loss of both alleles? Dr. Alison Schram: So we will get into what's unique about uterine sarcomas in just a minute. In uterine sarcomas, what we have found is that the BRCA mutations tend to be somatic and not germline, as you mentioned. That is in contrast to the other diseases we mentioned, where the vast majority of these tumors are in patients that have germline BRCA alterations. So one thing that's really unique about the uterine sarcoma population and our paper, I believe, is that it is demonstrating an indication for PARP inhibitors in a population that is not characterized by germline BRCA alterations, but truly these by somatic BRCA alterations. If you look at the diseases that PARP inhibitors are validated to be effective in, including the, you know, the ones I mentioned, the BRCA-associated tumors, there's some data in specific context that suggests that perhaps germline alterations are more sensitive to PARP inhibitors, but that's not universal, and it's really tricky to do because the genetic testing that we have doesn't always tell you if you have two hits or just one hit. So you need more complex genetic analysis to truly understand if there is what we call a biallelic loss. And sometimes it's not a second mutation in BRCA. Sometimes it's silencing of the gene by hypermethylation or epigenetics. Some of our clinical trials are now incorporating this data collection to really understand if biallelic loss that we can identify on more complex genetic testing predicts for better outcomes. And we think it's probably true that the patients that have biallelic loss, whether it be germline or somatic biallelic loss, are more likely to benefit from these treatments. That still needs to be tested in a larger cohort of patients prospectively. Dr. Rafeh Naqash: In your clinical experience, I know you predominantly use MSK-IMPACT, but maybe you've perhaps used some other NGS platforms, next-generation sequencing platforms. Have you noticed that these reports for BRCA alterations the report mentioning biallelic loss in certain cases? I personally don't- I do lung cancer, I do early-phase lung cancer as well, but I personally don't actually remember if I've seen a report that actually says biallelic loss. So after this podcast, I'm going to check some of those NGS reports and make sure I look at it. But have you seen it, or what would be a learning point for the listeners there? Dr. Alison Schram: Exactly. And they usually do not. They usually do not explicitly say, “This looks like biallelic loss,” on the reports. The exception would be if there's a deep deletion, then that implies both copies of the gene have been deleted, and so then you can assume that it's a biallelic loss. But oftentimes, when you see a frameshift alteration or a mutation, you don't know whether or not it's a biallelic loss. And you may be able to get some clues based on the variant allele frequencies, but due to things like whole genome duplication or more complex tumor genomics, it's not clear from these reports, and you really do need a more in-depth bioinformatic analysis to understand whether these are biallelic or not. So that is why I suggest that this really needs to be done in the context of a clinical trial, but there is definitely a theoretical rationale for reporting and treating patients with biallelic losses perhaps more so than someone who has a variant of unknown significance that seems to be monoallelic. The other tricky part, as I mentioned, is the fact that there could be epigenetic changes that silence the second copy, so that wouldn't be necessarily evident on a DNA report, and you would need more complex molecular testing to understand that as well. Dr. Rafeh Naqash: Sure. Now, going to your study, could you tell us what prompted the study, what was the patient population that you collected, and how did you go about this research study design? Dr. Alison Schram: It's actually a great story. I was the principal investigator for a clinical trial enrolling patients regardless of their tumor type to a combination of a PARP inhibitor and immunotherapy. And this was a large clinical trial that was being done as a basket study, as I mentioned, for patients that have either germline or somatic alterations with advanced solid tumors that had progressed on standard therapy. And the hypothesis was that the combination of a PARP inhibitor and immunotherapy would be synergistic and that there would be increased efficacy compared to either agent alone and that patients who had BRCA alterations were a sensitive population to test because of their inherent sensitivity to PARP inhibitors and perhaps their increased neoantigen burden from having loss of DNA repair. So this large study, it's been published, really did show that there was efficacy across several tumor types, but it didn't seem to clearly demonstrate synergy between the immunotherapy and the PARP inhibitor as compared to what you might expect from a PARP inhibitor alone, and in addition to a couple of cases, perhaps attributable to the immunotherapy. So maybe additive rather than synergistic efficacy. However, what really struck me looking at the data was that there were three patients with uterine leiomyosarcoma with BRCA deletions who had the best responses of anyone on the study. So incredible, durable responses. One of my patients with a complete response that continues to not have any evidence of cancer eight years after the initiation of this regimen. And for those of us that treat uterine leiomyosarcoma, this is unheard of. These patients generally, as I mentioned, respond, if they do respond to chemotherapy, it's generally short-lived and the cancer progresses. And so a complete response nearly a decade later turns heads in this field. The other interesting thing was that these uterine leiomyosarcoma patients had somatic alterations rather than a germline alteration with a second hit, and the diseases that are best validated for being responsive to PARP inhibitors include the BRCA-associated diseases, the ones that you're at increased risk for if you have a germline BRCA mutation, including breast, pancreas, prostate, and ovarian. And so it was very interesting that this disease type that seemed to be uniquely sensitive to PARP inhibitors with immunotherapy was also different in that patients with uterine leiomyosarcoma don't tend to have a high frequency of BRCA alterations, and in patients that are born with a BRCA alteration, there doesn't seem to be a clearly increased risk of uterine sarcomas. So this population really jumped out as a uniquely sensitive population that differed from the prior indications for PARP inhibitors. Given this patient and these couple of patients that we observed on the combination, in addition to some other case reports and case series that had started to come out in small numbers, we wanted to look back at our large cohort of patients at Memorial Sloan Kettering to see if we could really get a better sense of the numbers. How many patients at Sloan Kettering with uterine sarcomas have BRCA alterations? Are they generally somatic or germline? Are there unique features about these patients in terms of their clinical characteristics? How many of them have received PARP inhibitors, and if so, is this just luck that these three patients did so well, or is this really a good treatment option for patients with BRCA-altered uterine sarcomas? And so we did this retrospective analysis identifying the patients at Sloan Kettering who met these criteria. So in total, we found 35 patients with uterine sarcomas harboring BRCA alterations, and the majority were leiomyosarcoma, about 86% of them had leiomyosarcoma, which is interesting because there are other uterine sarcomas, but it does seem like BRCA alterations tend to be more often in the leiomyosarcomas. And 13 of these patients with uterine leiomyosarcoma were treated with PARP inhibitors in the recurrent or metastatic setting with about half of those patients having an overall response, so that's a significant tumor shrinkage that sustained, and a clinical benefit rate of 62%. And if we look at the patients that had these BRCA2 deep deletions, which was the patient I had that had this amazing response, the overall response rate jumped to 60% and the clinical benefit rate to 80%. And we defined clinical benefit rate as having maintained on the PARP inhibitor without evidence of progression at six months. So this is really impressive for patients with a difficult to treat disease. And we couldn't do a randomized controlled trial comparing it to chemotherapy, but looking retrospectively at outcomes on chemotherapy studies, this was very favorable, particularly because many of these patients were heavily pretreated. So to get a sense of, you know, how this might compare to chemotherapy, we tried to use patients as their own internal controls, and we looked at how long patients were maintained on the PARP inhibitor as compared to how long they were on the treatment just prior. And we used a ratio of 1.3 to say if they were on the PARP inhibitor for 1.3 times what their previous treatment was or longer, that is pretty clearly better, more of a benefit from that regimen. And the majority of patients did meet that bar. So 58% had a PFS ratio greater than 1.3, and the average PFS ratio was 1.9, suggesting, you know, you would expect the the later lines of therapy to actually not work as well, but this suggests that it's actually working better than the immediately prior line of therapy, to me, suggesting that this is truly a good treatment option for these patients. Dr. Rafeh Naqash: Very interesting. And you mentioned that individuals with tumors having deep deletions were probably more responsive. How did you figure out that there was biallelic loss or deep deletions? Was that part of an extended analysis that was done subsequently? Dr. Alison Schram: So the deletions reported on our report, if it's a biallelic deletion, that is the one biallelic molecular alteration that would be reported. So those are, by definition, biallelic, and I think that that may be one of the reasons that's a good biomarker. But also, what's interesting is that if you have both copies deleted of BRCA, you can't develop reversion mutations. So one of the the known mechanisms of resistance to PARP inhibitors in patients who have BRCA alterations are something called a reversion mutation where, if you have a frameshift alteration, for example, in BRCA that makes BRCA protein nonfunctional, you can develop a second mutation that actually puts the DNA back in frame, and a functional protein is now made. And so a mechanism of resistance to PARP inhibitors is actually reverting BRCA to a wild-type protein, and then BRCA's synthetic lethality no longer makes sense and is no longer effective. But if you've deleted both copies of BRCA, you don't have the ability to restore the function, and you can't develop reversion mutations. And that's perhaps why, you know, my patient and others have had these prolonged responses to PARP inhibitors because you don't have the same ability to develop that mechanism of resistance. Dr. Rafeh Naqash: I remember thinking a year and a half back, I had an individual with prostate cancer and with BRCA2, and using liquid biopsy, I had a reversion mutation that we caught. In your practice, have you seen the utility of doing the serial liquid biopsies in these individuals to catch these reversion mutations? Dr. Alison Schram: Yes, absolutely. And in patients that have the ability to develop a reversion mutation, serial cell-free DNA can catch it, but the caveat is that it doesn't always. So if you see an acquired reversion mutation in cell-free DNA, that can be helpful, particularly if you're planning on putting the patient on another line of therapy that might require a dysfunctional BRCA. So if you're putting them on a clinical trial with a PARP combination and the rationale is that they're sensitive because they don't have a functional BRCA, you would want to know if they developed a reversion mutation, and serial cell-free DNA can definitely identify these reversion mutations. Some of the major clinical trials in ovarian cancer have done serial cell-free DNA and have demonstrated the utility of that approach. The caveat is that some of these reversion mutations are not readily caught on cell-free DNA because they're more complex reversion mutations, or they're not, the part of the gene that develops the reversion mutation is not tiled on the panel. And so it doesn't always catch the reversion mutations. Also, depends on the cell-free DNA shedding, depends on the tumor volume and other factors. And we published a related paper of a patient, it was a really interesting case of a patient with prostate cancer who was on a PARP inhibitor and developed what appeared to be a single reversion mutation on one sample, had negative cell-free DNA, single reversion mutation in a tissue biopsy, and then developed disease progression. And we did an autopsy, and the patient kindly consented to an autopsy, and at the time of autopsy, there were 10 unique reversion mutations identified across 11 metastases. So almost each metastasis had a unique reversion mutation, and only one of them had been seen premortem on a tissue biopsy and not on a cell-free DNA. But that autopsy really drove home to me how much we're missing by doing clinical testing in real time and we really don't know the entire genomic complexity of our patients by doing single samples. And theoretically, cell-free DNA can catch DNA from all the metastases, so you might think that that would be a solution, and it definitely can catch reversion mutations that are not seen in a single biopsy, but you really need to do it all. I mean, you need to do the tissue biopsy sampling, you need to do cell-free DNA, and probably one cell-free DNA test is not enough. Dr. Rafeh Naqash: Thank you, again, for that very nice explanation. Now, one quick provocative question. I remember when I was training, the lab that I used to work in, they used to do a lot of phosphorylation markers for DNA damage response, like phospho NBS, RAD51. Have you seen anything of that sort on these biallelic BRCA mutations where tumors are responding, but they also have a very high signature on the phosphorylation side, and it may or may not necessarily correspond to HRD signatures, but have you noticed or done any of that analysis? Dr. Alison Schram: I think that it would be great to do that analysis. And some of the work we're doing now is actually trying to dig a little bit deeper in our cohort of patients to understand are these HRD-positive tumors? Does HRD positivity correlate with response to BRCA alterations? In terms of the functional assays, I would love to be able to do a functional assay in these samples. One of the challenges is that this was a retrospective study and many of the patients were previously treated as standard of care or off-label with these agents, and so we didn't have prospective tissue collection, and so we're really limited by the tissue that was collected as part of standard of care and the consent forms that the patient signed that allow us to do genomic and molecular testing on their samples. So, I think that is hopefully future work that we will do and others will do. Dr. Rafeh Naqash: Sure. Shifting gears to your career trajectory, I'd like to spend a couple of minutes there before we end the podcast. So Dr. Schram, you've obviously been a trailblazer in this space of drug development, early-phase trials. Can you give us a brief synopsis of your journey and how you've successfully done what you're doing and what are some of the things that drive you? Dr. Alison Schram: Well, thank you for saying that. I don't know if that's true, but I'll take the bait. I've been interested in oncology since college and was always very interested in not only the science of oncology but of course, treating patients. And in medical school, I did basic science research in a laboratory and it was very inspiring and made me want to do research in oncology in addition to clinical care. When I became an oncology fellow, I was presented with a very difficult question, which is, “Do you want to be a lab PI and be in the lab, or do you want to do clinical care and clinical research?” And I couldn't choose. I found a mentor who thankfully really had this amazing vision of combining the two and doing very early drug development, taking the data that was being generated by labs and translating it into patients at the earliest stage. So, you know, phase one drug development in molecularly targeted therapies. And so I became very interested as a fellow in early drug development and this ability to translate brand new molecular insights into novel drugs. And I joined the- at Sloan Kettering, there was the Early Drug Development, it was actually a clinic, it was called something different, and it was very fortuitous. My last year of fellowship, the clinic became its own service with the ability to hire staff at Sloan Kettering, and I was the first ever hire to our Early Drug Development Service. And that really inspired me to try and bring these drugs to patients and to really translate the amazing molecular insights that my colleagues here at Sloan Kettering are discovering, and you know, of course, at other institutions and in pharma. And you know, there 's been an amazing revolution in in drug development over the last several years, and I feel very grateful that I've been here for it. You know, I've been able to take the brilliant insights from my colleagues and put these drugs in patients, and I have the amazing privilege of watching patients in many cases that benefit from these treatments. And so I do mostly phase one drug development and molecularly targeted therapies, and truthfully, I am just very fortunate to be around such brilliant people and to have both patients and labs trust me to be able to deliver these new drugs to patients and hopefully develop better drugs that move forward through FDA approval and reach patients across the country. Dr. Rafeh Naqash: Thank you so much. That was very nicely put. And hopefully our trainees and junior faculty find that useful based on their own career trajectories. Thank you, Dr. Schram, for joining us today. Hopefully, we'll see more of your subsequent work in JCO PO. Thank you for giving us all these insights today. Dr. Alison Schram: Thank you for having me. 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. Dr. Alison Schram Disclosures Consulting or Advisory Role Company: Mersana, Merus NV, Relay Therapeutics, Schrodinger, PMV Pharma ,Blueprint Medicines, Flagship Pioneering, Redona Therapeutics, Repare Therapeutics, Endeavor BioMedicines Research Funding Company: Recipient: Your Institution  Merus, Kura, Surface Oncology, AstraZeneca, Lilly, Pfizer , Black Diamond Therapeutics, BeiGene, Relay Therapeutics, Revolution Medicines,  Repare Therapeutics, PMV Pharma, Elevation Oncology, Boehringer Ingelheim Travel, Accommodations, Expenses Company: PMV Pharma 

PCR has been a staple of molecular biology for over 30 years. But as Yann Jouvenot, Director of Product at N6 Tec, explains, no technology is ever too mature to be reinvented. In this walk and talk interview along the Martinez (CA) shoreline, we explore how N6 Tec's ICON PCR technology is reshaping genomics workflows: reducing artifacts, unlocking discoveries at the margins, and giving postdocs their nights back.The Problem with OveramplificationNext-generation sequencing (NGS) has revolutionized biology, but library preparation still relies heavily on PCR. While PCR is essential for generating enough DNA to sequence, too many cycles introduce errors and distortions in the results. Abundant samples may only need a handful of cycles, but low-quality or scarce DNA, such as from liquid biopsies, requires more amplification. If one demands more cycles for all samples, that increases the risk of duplicates and bias in some.Overamplification can suppress the detection of rare or structurally complex sequences. This means that some species or genetic variants simply disappear from view if a sample is cycled too many times. That forces scientists into a tough choice between two suboptimal scenarios:* Overamplify samples and accept the consequences: duplicates, errors, distorted representation.* Babysit reactions manually: pausing machines at just the right time, tube by tube, cycle by cycle.The ICON PCR BreakthroughTraditional PCR machines heat an entire metal block of wells at once, forcing all reactions to follow the same program. ICON PCR takes a different approach: instead of one block, it has 96 individually controlled heating elements with sensors—effectively 96 thermocyclers in the space of a standard plate. Each well can stop cycling the moment its target threshold is reached, while others continue until they are done.I geeked out for a bit on the engineering aspect of this story. This design required immense effort to miniaturize components and coordinate heat, power and amplification detection for each well. The result is transformative: wells act independently without affecting their neighbors. One reaction can continue as normal, while the eight “cooler neighbors” around it have finished and are held at low temperature. Yann joked about “Cooler Neighbors” sounding like the name of a new sitcom.Where and Why It Matters* Metagenomics: ICON PCR preserves diversity by preventing dominant species from overwhelming rare ones. In studies of soil samples, ICON PCR identified 5–10 times more species than conventional workflows.* Liquid Biopsies & Preventive Healthcare: As sequencing capacity grows, the bottleneck shifts to library prep. ICON PCR's AutoNorm™ feature automatically normalizes libraries, reducing the need for individual purification and quantification. This saves time, consumables, and labor while improving downstream data quality.* Reducing Hidden Costs: Overamplification generates duplicate reads and useless data, which labs still pay to store. By reducing noise at the source, ICON PCR helps avoid paying for “garbage in the cloud.”Looking AheadYann sees ICON PCR as a key enabler for the future of liquid biopsies and preventive healthcare, where cost-effective and accurate sequencing will become routine. He also points to the broader promise of tools that let us see biological systems holistically, rather than through narrow markers. Just as early discoveries like Taq polymerase unexpectedly transformed entire industries, advances like ICON PCR may open new scientific and diagnostic horizons.The Human ImpactBeyond cost savings, Yann emphasizes something often overlooked: the scientist's experience. Postdocs have long wasted hours hovering over reactions, pausing machines to remove individual tubes. With ICON PCR, they can simply set a fluorescence threshold, walk away, and trust the system. That reclaimed time could mean more science or more poetry, music, and life outside the lab.Your deepest insights are your best branding. I'd love to help you share them. Chat with me about custom content for your life science brand. Or visit my website. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

In this episode of The Underground Podcast, Phil and Kate welcome Anna Wili, Head of Marketing for the National Garden Scheme (NGS), a charity with almost a century of history opening gardens for good causes. Anna shares how the NGS began in 1927 as a way to fund district nursing, and how it's grown to over 3,500 gardens opening each year, raising more than £74 million for nursing and health charities.We explore the unique blend of horticulture, hospitality, and heart that makes garden visiting so special. From peeping behind rarely opened gates to enjoying a slice of homemade cake. Anna reveals how the NGS champions the link between gardens and wellbeing, the variety of gardens that take part (from manicured estates to wildlife havens), and the personal stories that bring each opening to life.With the charity's centenary celebrations in 2027 on the horizon, Anna also outlines exciting plans for brand partnerships with the garden industry, opportunities for garden centres and suppliers, and how professionals across the sector can get involved.Whether you're a garden centre owner, a manufacturer, or simply a passionate gardener, this episode is packed with insights into:How the NGS sustains a 100-year tradition of generosity and community spiritThe role of gardens in health, biodiversity, and wellbeingOpportunities for collaboration and brand licensing in the run-up to the centenaryHow to become an NGS garden owner and why you shouldn't be shy about your patchAnd of course, we discover which celebrity Anna would most like to see open their garden for charity…Listen in and be inspired to throw open your own garden gates or work with the NGS to help them grow their impact even further.National Garden Scheme: https://ngs.org.uk/Your hosts:Phil Wright: ⁠⁠http://wrightobara.com⁠⁠Kate Turner: ⁠⁠http://www.gardenerguru.co.uk

Welcome to the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain, practicing community oncologists, share their key takeaways from a session on NTRK Fusion Positive Solid Malignancies, they moderated during a satellite event at ASCO 2025 in partnership with Medscape Global Oncology. Join us as we discuss: •⁠  ⁠The prevalence of NTRK fusions in various cancers and why community oncologists should be aware of them. •⁠  ⁠The importance of comprehensive next-generation sequencing (NGS) for detecting these fusions across diverse histologies. •⁠  ⁠Available treatment options, including first-generation NTRK inhibitors like larotrectinib and entrectinib, and their efficacy in improving overall and progression-free survival. •⁠  ⁠Insights into the CNS activity of these treatments and the common side effects patients may experience. •⁠  ⁠Special considerations for pediatric patients, including formulation challenges and the potential for re-challenging with NTRK inhibitors. Don't forget to check out the full accredited enduring program by Medscape Global Oncology linked below, and earn your CME credit.  https://www.medscape.org/viewarticle/1002679?src=acdmpart_onc-brothers_1002679  Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ #entrectinib #larotrectinib #repotrectinib

“Next-generation sequencing, or NGS, can be used to help us determine if the patient has specific biomarkers we can identify and use to target for treatment. Certain findings can tell us if a particular treatment might work for that patient, and we can see if there are any genetic variants we might have a biomarker targeted agent to use to treat them with,” ONS member Jackie Peterson, MSN, RN, OCN®, NE-BC, MBA, ambulatory nurse manager at the University of Chicago Medical Center in Illinois, told Lenise Taylor, MN, RN, AOCNS®, BMTCN®, oncology clinical specialist at ONS, during a conversation about prostate cancer and biomarker testing.  This podcast is sponsored by AstraZeneca and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications.   Music Credit: “Fireflies and Stardust” by Kevin MacLeod    Licensed under Creative Commons by Attribution 3.0   Episode Notes This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 324: Pharmacology 101: LHRH Antagonists and Agonists Episode 321: Pharmacology 101: CYP17 Inhibitors Episode 180: Learn How Nurse Practitioners Use Biomarker Testing in Cancer Care ONS Voice articles: An Oncology Nurse's Guide to Cascade Testing Genetic Disorder Reference Sheet: BRCA1 and BRCA2 Hereditary Disorders Genetic Disorder Reference Sheet: Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Germline and Somatic Variants: What Is the Difference? Help Patients Understand Genomic Variants of Unknown Significance Prostate Cancer Clinical Trials Don't Reflect Racial Diversity—And It's Getting Worse Over Time Prostate Cancer Disparities Disappear With Equal Access to Care Prostate Cancer Prevention, Screening, Treatment, and Survivorship Recommendations The Case of the Genomics-Guided Care for Prostate Cancer ONS book: Understanding Genomic and Hereditary Cancer Risk: A Handbook for Oncology Nurses ONS course: Genomic Foundations for Precision Oncology Clinical Journal of Oncology Nursing articles: Metastatic Prostate Cancer: An Update on Treatments and a Review of Patient Symptom Management Prostate Cancer: How Nurse Practicioners Can Aid in Disease Diagnosis and Management Oncology Nursing Forum article: Identification of Symptom Profiles in Prostate Cancer Survivors Other ONS Resources: Biomarker Database (refine by prostate cancer or specific biomarkers) Clinical tool/case study: Biomarker Testing in Prostate Cancer: The Role of the Oncology Nurse Genomics and Precision Oncology Learning Library Huddle Card: Genomic Biomarkers Infographic: Talking to Your Patient About a Germline Variant of Uncertain Significance (VUS) American Cancer Society - Genetic Testing and Counseling for Prostate Cancer Risk American Cancer Society - Prostate Cancer Clinicaltrials.gov National Cancer Institute - Prostate Cancer National Comprehensive Cancer Network ZERO Prostate Cancer To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.  Highlights From This Episode “Some of the risk factors for developing prostate cancer include age, race, family history, and certain genetic changes or variants. Prostate cancer has some hereditary components, but most prostate cancer occurs in men without any significant family history of it.” TS 1:31 “Key biomarkers include PSA and prostate cancer gene 3, which is PCA3, and prostate-specific membrane antigen, or PSMA. Other biomarkers that are important for us to test include BRCA1, BRCA2, and Lynch syndrome–associated genes, which are MLH1, MSH2, MSH6, PMS2, and EPCAM. Biomarkers can be collected via your blood, urine, saliva, or tissue samples, so these are different ways that we can test and look for biomarkers in our patients.” TS 3:24 “It does matter how advanced the disease is. Usually, for our castrate-sensitive patients, they respond better to androgen deprivation therapy because that really is slowing down the growth of the cancer by reducing the available testosterone that the cancer needs to grow. Whereas our patients that are more advanced and have castrate-resistant prostate cancer, that cancer will continue to grow despite having the lowered testosterone levels, so they might need additional layers of treatment to really get their cancer under control.” TS 7:50 “When I talk to [patients] about biomarker testing, I tell them it's another tool in our toolbox that we can use to help us determine if they might benefit from other therapy options now or in the future. I tell them that sometimes we'll get a report back with a variant of unknown significance, and basically that means that we don't really know whether or not this has an impact on their health or risk factors for the disease. That can sometimes be a little bit of a concern for these patients, so we just have to reassure them that we're continually doing research around biomarker testing. The science is always advancing, so if there's something that [researchers] find in the future, we'll make them aware of that.” TS 9:08 “One of the biggest topics I think about is the inequity that exists in biomarker testing and research, especially surrounding the African American population. When these tests were developed, that population really wasn't studied as much, so there's not a lot of good data yet to make a decision or impact on those patients and that population.” TS: 12:30

Welcome to the Paint The Medical Picture Podcast, created and hosted by Sonal Patel, CPMA, CPC, CMC, ICD-10-CM.Thanks to all of you for making this a Top 15 Podcast for 4 Years: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://blog.feedspot.com/medical_billing_and_coding_podcasts/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Sonal's 15th Season starts up and Episode 12 features a Newsworthy spotlight on the Medicare Physician Fee Schedule Proposed Rule for CY 2026.Sonal's Trusty Tip and compliance recommendations focus on NGS' top claim error codes.Spark inspires us all to reflect on hopes and aspirations based on the inspirational words of Jonas Salk.MPFS Proposed Rule for CY 2026:Proposed Rule: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://public-inspection.federalregister.gov/2025-13271.pdf?1752524111⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Paint The Medical Picture Podcast now on:Spotify: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://open.spotify.com/show/6hcJAHHrqNLo9UmKtqRP3X⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Apple Podcasts: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://podcasts.apple.com/us/podcast/paint-the-medical-picture-podcast/id153044217⁠7⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Amazon Music: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://music.amazon.com/podcasts/bc6146d7-3d30-4b73-ae7f-d77d6046fe6a/paint-the-medical-picture-podcast⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Find Paint The Medical Picture Podcast on YouTube: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.youtube.com/channel/UCzNUxmYdIU_U8I5hP91Kk7A⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Find Sonal on LinkedIn:⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.linkedin.com/in/sonapate/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠And checkout the website:⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://paintthemedicalpicturepodcast.com/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠If you'd like to be a sponsor of the Paint The Medical Picture Podcast series, please contact Sonal directly for pricing: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠PaintTheMedicalPicturePodcast@gmail.com⁠⁠⁠⁠

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. Takeda has taken the lead in the race for a narcolepsy treatment with back-to-back phase III wins for their drug Oveporexton. Investors are eagerly awaiting breakthroughs in using psychedelics to treat depression. Ultragenyx faced a setback as the FDA rejected their gene therapy for Sanfilippo syndrome, citing manufacturing issues. The FDA is considering speeding up reviews for companies that promise to lower drug costs. Market reaction to recent readouts from Compass Pathways and Beckley Psytech/Atai in treatment-resistant depression shows the challenges psychedelic therapies must overcome for commercial viability. Rainin Micropro offers a solution to streamline NGS preparation with their 96-channel pipettor. The industry is also focused on precision diagnostics to support precision therapeutics in the future. AstraZeneca's Baxdrostat showed promising results in lowering blood pressure in a phase III trial. The ADA revealed R&D priorities for potential blockbuster obesity treatments. Relmada has abandoned development of a depression drug after three failed attempts.The challenges faced by psychedelic therapies in the treatment of depression are discussed, as recent readouts from Compass Pathways and Beckley Psytech/Atai in treatment-resistant depression have left investors wanting more. The market reaction highlights the hurdles psychedelic therapies must overcome to prove their commercial viability. Additionally, the importance of precision diagnostics in the development of next-generation precision oncology therapies is emphasized, stating that only with the adoption of digital imaging and AI-powered analysis will these therapies reach their full potential. The FDA has several important decisions lined up, including applications in lymphoma, rare diseases, and hormone deficiency, while the American Diabetes Association's annual meeting reveals R&D priorities for weight loss medicines. Topics discussed include Capricor's FDA rejection of a DMD cell therapy, the ALS community petitioning the FDA to reconsider Brainstorm's Nurown, and updates on COVID-19 vaccines and Alzheimer's drugs. Upcoming webinars and job opportunities in the biopharma industry are also included.

BUFFALO, NY - July 7, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience.” In this study, a research team led by first author Fei Fei and corresponding author Michelle Afkhami from the City of Hope Comprehensive Cancer Center investigated a rare and aggressive type of blood cancer called blastic plasmacytoid dendritic cell neoplasm (BPDCN). Their research uncovered frequent mutations in key genes and identified CCDC50 as a potential biomarker for diagnosis and disease monitoring. These findings could help improve how this cancer is detected and treated in the future. BPDCN most often affects older adults and is known for its rapid progression and poor survival rates. The researchers performed genetic sequencing on 21 patients to better understand the disease. They found that two genes, TET2 and ASXL1, were frequently mutated in these patients and were linked to worse survival, especially in those over 65 years old. “Our study revealed that TET2 (57%) and ASXL1 (33%) were the most frequently mutated genes, followed by NRAS (29%), SRSF2 (14%), ZRSR2 (14%), and KMT2D (14%).” The study also discovered that a gene called CCDC50 was expressed at much higher levels in BPDCN samples compared to other blood cancers, such as acute myeloid leukemia and chronic monomyelocytic leukemia. This suggests that CCDC50 may help clinicians distinguish BPDCN from other similar diseases. Importantly, CCDC50 levels dropped significantly in patients whose disease went into remission, highlighting its potential as a tool for tracking disease activity over time. Researchers further observed that patients who received stem cell transplants lived longer than those who did not, reinforcing the importance of this treatment approach. However, BPDCN remains a challenging disease with an overall poor outlook, making these findings an important step toward better care. This research provides new insights into the genetic changes behind BPDCN and points to CCDC50 as a promising marker to improve diagnosis and monitor treatment success. Larger studies will be needed to confirm these results and bring these discoveries closer to use in routine medical practice. DOI - https://doi.org/10.18632/oncotarget.28742 Correspondence to - Michelle Afkhami - mafkhami@coh.org Video short - https://www.youtube.com/watch?v=wUjr3uU3onI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28742 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50 To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

NGS 105 – How Charismatic Men Handle Women Who Make It Hard to Set a Date

Originally employed in atomic physics, mass spectrometry is now an indispensable tool in modern science, and importantly medical science. In a new pharmaphorum podcast, web editor Nicole Raleigh spoke with Melissa Sherman, CEO of MOBILion Systems, a company pioneering next-generation separation science, by innovating best-in-class instruments that deeply, accurately, and efficiently characterise complex molecules. Sherman discusses the practical impact of this new technology for R&D, MOBILion's work with mass spectrometry technology at the moment, and the future horizon for this and NGS. You can also listen to episode 186a of the pharmaphorum podcast in the player below, download the episode to your computer, or find it - and subscribe to the rest of the series – on Apple Podcasts, Spotify, Overcast, Pocket Casts, Podbean, and pretty much wherever else you download your other podcasts from.

Join the National Galleries of Scotland (NGS) as they celebrate Pride Month by delving into queer stories within the collection. Amelia spoke to Meg Faragher, from the learning & Engagement team, to learn more. Learn more about the session on the NGS website - Visually Impaired Programme (Online) | Queer stories in art | National Galleries of Scotland Access to this session will be via Zoom. A telephone number, link and password will be sent out before the session. To book a free place, please use online booking or contact us on 0131 624 6410 or learning@nationalgalleries.org. Image shows the RNIB Connect Radio logo. On a white background ‘RNIB' written in bold black capital letters and underline with a bold pink line. Underneath the line: ‘Connect Radio' is written in black in a smaller font. 

In this episode of Speaking of Mol Bio, Dr. Cath Moore of the Australian Genome Research Facility (AGRF) discusses how molecular biology technologies are helping to shape Australia's scientific landscape—from clinical genomics and conservation to bioremediation and agriculture. With over 20 years of experience in both academia and industry, Dr. Moore reflects on the remarkable evolution of genomic tools, from Sanger sequencing to high-resolution spatial multiomics.She unpacks AGRF's mission to democratize access to emerging technologies and highlights its role as an early adopter of platforms that help scientists translate academic research into real-world impact. Topics include non-mass spec proteomics, mine site rehabilitation through soil microbiome analysis, and the role of systems biology in modern science.Dr. Moore also discusses the importance of community education and literacy around genomics, emphasizing how public understanding is key to the safe adoption of emerging technologies like synthetic biology. Finally, she shares career insights and advice for aspiring scientists: stay curious, stay broad, and don't be afraid to pivot when your work no longer brings joy. Subscribe to get future episodes as they drop and if you like what you're hearing we hope you'll share a review or recommend the series to a colleague.  Visit the Invitrogen School of Molecular Biology to access helpful molecular biology resources and educational content, and please share this resource with anyone you know working in molecular biology. For Research Use Only. Not for use in diagnostic procedures.

Spring is the season when gardeners throw off the hibernation and slumber of months of wet feet, many layers and waterproofs and are reborn anew! The stirring of life in the garden is one of the years great experiences, and makes a gardening life such a worthwhile pursuit, not only is it good for the planet to see the earth greening up, it is also good for the gardeners soul. But there is still lots of hard work to get on with - seeds have to be sown, mulch laid, supports erected and lawns mown. So join Lucy and Saul as they continue their professional gardening lives in the pure heaven that is Spring!With no rain on the horizon for Lucy and plenty for Saul, the East - West divide is playing out true to form. But other traditionally damper UK regions are also experiencing dry weather, giving the gardening duo plenty to talk about. Musing aside, Saul has been busy erecting bamboo canes, whilst Lucy has been wielding her saws and fine-tuning her ears to local birdsong. Mr Walker can also now celebrate his first decade as a Head Gardener - congratulations, Mr W! Let's hope the NGS group left you a decent slice of cake on Thursday.LinkedIn link:Saul WalkerInstagram link:Lucy lucychamberlaingardensIntro and Outro music from https://filmmusic.io"Fireflies and Stardust" by Kevin MacLeod (https://incompetech.com)License: CC BY (http://creativecommons.org/licenses/by/4.0/)Support the show

Join us in this episode of the Oncology Brothers podcast as we dive deep into the rapidly evolving treatment landscape for metastatic non-small cell lung cancer (NSCLC) with actionable mutations in frontline therapy. Hosted by community oncologists Drs. Rahul and Rohit Gosain, we are thrilled to welcome Dr. Susan Scott, a thoracic medical oncologist from the Johns Hopkins Hospital. In this episode, we covered: •⁠  ⁠Common EGFR mutations and the latest treatment options, including osimertinib, amivantamab, and chemotherapy combinations. •⁠  ⁠The importance of comprehensive NGS testing and the need for retesting at progression. •⁠  ⁠Insights into managing side effects associated with various therapies, including the proactive management of cutaneous toxicities. •⁠  ⁠Treatment strategies for less common mutations such as ALK, ROS1, BRAF, and RET, along with their respective targeted therapies. •⁠  ⁠The role of immunotherapy in specific mutations and the importance of patient choice and preferences in treatment decisions. Whether you're a practicing oncologist or simply interested in the latest advancements in cancer treatment, this episode is packed with valuable information to help guide your practice. YouTube: https://youtu.be/LMYDAjZcn5w Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers!

This is the latest episode of the free DDW narrated podcast, titled “Cutting-edge tools shaping early-stage drug discovery”, which covers three articles written for DDW Volume 24 – Issue 4, Fall 2023. They are called: “The use-case for NGS”, “Are organ-chips the future of preclinical research?” and “What spatial biology can tell us about disease and drug discovery”. In the first article, DDW Editor Reece Armstrong speaks to Dr Darrell Green, Lecturer in RNA Biology, Biomedical Research Centre, Norwich Medical School University of East Anglia, about his work using next generation sequencing (NGS) and the areas the technology is impacting within drug discovery and development. In the second article, Diana Spencer catches up with Lorna Ewart, PhD, Chief Scientific Officer of Emulate, about the rise of organ-on-a-chip technology. In the third article, DDW Editor Reece Armstrong speaks to Benedikt Nilges, Head of Technology and Data Analytics at OMAPiX about spatial biology's use in drug discovery and bettering our understanding of disease.

Welcome to the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Mark Awad, a world-renowned thoracic medical oncologist from Memorial Sloan Kettering. Together, they dived deep into the treatment landscape for metastatic non-small cell lung cancer (NSCLC) without actionable mutations in frontline settings. Episode Highlights: •⁠  ⁠The importance of next-generation sequencing (NGS) and PD-L1 levels in treatment decision-making. •⁠  ⁠Current treatment options for patients with high PD-L1 scores, including single-agent immunotherapy. •⁠  ⁠Strategies for patients with low or intermediate PD-L1 scores, including chemotherapy combined with immunotherapy. •⁠  ⁠Discussed KRAS G12C and HER2 positive disease in second-line settings, including the latest approved therapies. •⁠  ⁠Insights into the potential side effects and considerations when transitioning from immunotherapy to targeted therapies. Join us as we explored the complexities of treating metastatic NSCLC and the ongoing need for clinical trials and biomarker discovery. Don't forget to check out our other episodes for more insights on treatment algorithms and recent FDA approvals! Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers!

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rohit and Rahul Gosain, both practicing community medical oncologists, continue their discussion on HER2-positive biliary tract cancer. They are joined by Dr. Shubham Pant from MD Anderson, who shares his expertise on this rapidly evolving field. In this episode, we cover: •⁠  ⁠The importance of HER2 testing in biliary tract cancers, including intrahepatic and extrahepatic cholangiocarcinomas and gallbladder cancers. •⁠  ⁠Who should be tested for HER2 positivity and how to classify HER2-positive disease. •⁠  ⁠The role of next-generation sequencing (NGS) and immunohistochemistry (IHC) in determining HER2 status. •⁠  ⁠Current treatment options for HER2-positive biliary tract cancer, including the latest clinical trials and approved therapies like trastuzumab deruxtecan and zanidatamab. •⁠  ⁠The significance of patient-centered decision-making and managing side effects associated with these treatments. •⁠  ⁠Insights into the potential for brain metastases in biliary tract cancer and the importance of ongoing surveillance. Join us as we delve into the latest data and strategies for managing HER2-positive biliary tract cancer, and stay tuned for our next episode where we will discuss side effects and management of these therapies. Accreditation/Credit Designation Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Acknowledgment of Commercial Support This activity is supported by an educational grant from Jazz Pharmaceuticals, Inc. Link to gain CME credits from this activity: https://www.gotoper.com/courses/from-bench-to-bedside-paradigm-shifts-in-her2-metastatic-btc-treatment Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers!

This is the second episode of a two-part series on the HER2 diagnostic and treatment landscape in non-small cell lung cancer (NSCLC), hosted by the Oncology Brothers, Drs Rohit and Rahul Gosain.      In this episode, Dr Isabel Preeshagul and Dr Eric Singhi provide the benefit of their experience when discussing how to approach different treatment scenarios in HER2-mutant NSCLC.   The conversation unfolds to cover: • Ways to distinguish HER2 alterations from other alterations on biomarker reports  • The latest efficacy and safety data of currently approved and emerging treatments for HER2-altered NSCLC   • The potential CNS activity of these treatments in patients with HER2-mutated NSCLC  • How the treatment pathway may look in the near future      Clinical takeaways • In NSCLC, HER2-positivity includes mutations, amplifications and overexpression. It's important to distinguish HER2 alterations from EGFR mutations, particularly exon 20 insertions, when interpreting next-generation sequencing (NGS) results  • Trastuzumab Deruxtecan (T-DXd) is currently the only approved targeted agent for HER2-altered NSCLC in the 2nd-line setting. It shows promising efficacy, especially in HER2-mutant cases, but has limited brain penetration and is associated with notable side effects, including pneumonitis, which requires close monitoring  • Emerging TKIs, such as zongertinib, BAY 2927088 (sevabertinib), and NVL-330, target HER2-mutations and have shown high response rates and CNS activity in early studies, without ILD/pneumonitis. These treatments come with unique side effects like diarrhoea and rash, which can be managed with supportive care  • CNS metastases are common, with up to 30% of HER2-altered NSCLC patients presenting with or quickly developing CNS metastases. Current large molecule therapies (like T-DXd) have limited brain penetration, making small-molecule TKIs, like zongertinib, BAY 2927088 (sevabertinib), and NVL-330, promising for their potential CNS activity • Current standard 1st-line care for HER2-mutant NSCLC remains platinum-based chemotherapy ± immunotherapy. Targeted agents (like T-DXd) are generally reserved for 2nd-line use, but ongoing trials are evaluating the move toward frontline therapy Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for the next episode

Send us a textCan embryos labeled as “abnormal” still lead to healthy babies? Are fertility clinics discarding embryos that could result in a pregnancy?In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols breaks down the controversy surrounding Preimplantation Genetic Testing for Aneuploidy (PGT-A). You've seen the headlines — abnormal embryos resulting in live births — but was the test actually wrong, or was it the interpretation?Learn the truth behind PGT-A and mosaicism, the evolution of embryo testing methods (FISH, aCGH, SNP, and NGS), and what the latest data says about success rates when transferring embryos diagnosed as aneuploid.Whether you're trying to understand your PGT-A results, deciding whether to transfer a mosaic embryo, or just looking for clarity in a confusing area of IVF science, this episode is your guide.

Join us for an insightful episode of the Oncology Brothers podcast as we dive into the fast-evolving landscape of HER2-positive non-small cell lung cancer (NSCLC). In this first part of the two-part series, Drs. Rahul and Rohit Gosain were joined by Dr. Devika Das, a thoracic medical oncologist, and Dr. Fernando Lopez-Rios, a pathologist, to discuss the critical importance of testing and identifying HER2 alterations in lung cancer patients. In this episode, we covered: •⁠  ⁠The significance of HER2 alterations in NSCLC and how they differ from breast and gastric cancers. •⁠  ⁠The complexities of biomarker testing, including NGS, IHC, and FISH amplification. •⁠  ⁠Patient characteristics and phenotypes associated with HER2-positive disease. •⁠  ⁠The current testing workflows in clinical practice and the role of liquid biopsies. •⁠  ⁠Insights into the treatment landscape for HER2-positive NSCLC, including recent FDA approvals and ongoing clinical trials. Whether you're a healthcare professional or simply interested in the latest advancements in oncology, this episode provides valuable information on the integration of precision medicine in lung cancer treatment. YouTube: https://youtu.be/gMi-sflQyQo Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for the next episode, where we will explore treatment options for HER2-positive non-small cell lung cancer in greater detail!

Welcome back to the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Joshua Sabari, a thoracic medical oncologist from NYU, to discuss the latest findings from the European Lung Cancer Conference (ELCC) 2025. We dived into several key studies that are shaping the future of lung cancer treatment, including: • KEYNOTE-799: Exploring the combination of concurrent chemotherapy and radiation with the PD-1 inhibitor pembrolizumab for unresectable non-small cell lung cancer (NSCLC). • LAURA: The impact of osimertinib in patients with EGFR mutations post-chemoradiation therapy. • MARIPOSA: The promising results of amivantamab and lisertinib in the metastatic setting for EGFR-mutated NSCLC. • KRYSTAL-7: Investigating the use of KRAS G12C inhibitors in frontline therapy. Join us as we discuss the implications of these studies, the importance of next-generation sequencing (NGS), and how to manage side effects associated with these new therapies. YouTube: https://youtu.be/akoXXAUEl_8 Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates on the latest in oncology! #Oncology #LungCancer #ELCC2025 #EGFR #KRAS #CancerResearch #Podcast

Join us in this insightful episode of the Oncology Brothers podcast as we dive deep into the current treatment landscape of pancreatic cancer. Drs. Rohit and Rahul Gosain are joined by Dr. Emil Lou, a medical and neuro-oncologist from the University of Minnesota, to discuss the challenges and advancements in managing this complex disease. In this episode, we covered: •⁠  ⁠The importance of a multidisciplinary approach in treating early-stage pancreatic cancer. •⁠  ⁠The role of neoadjuvant and adjuvant therapies, including the latest insights on chemotherapy regimens like FOLFIRINOX, nal-IRI and gemcitabine. •⁠  ⁠The significance of germline and next-generation sequencing (NGS) testing in personalizing treatment plans. •⁠  ⁠The current state of clinical trials and emerging therapies, including PARP inhibitors for BRCA mutations and the implications of ctDNA testing. •⁠  ⁠Prognostic discussions around metastatic pancreatic cancer and the importance of managing side effects to improve patient quality of life. Key takeaways include the necessity of balancing treatment efficacy with adverse events, the critical role of genetic testing, and the need for vigilance regarding venous thromboembolism (VTE) in pancreatic cancer patients. Don't miss this comprehensive discussion that aims to shed light on the ongoing efforts to improve outcomes for patients battling pancreatic cancer.   YouTube: https://youtu.be/HCKQxmOqRTI   Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Subscribe to our channel for more discussions on oncology and stay updated on the latest in cancer treatment!

The field of Microbiology continues to change. Organisms were primarily identified in the clinical laboratory by biochemical testing. Then MALDI-TOF came to the lab and was incorporated into the workflow. Now labs are bringing next-generation sequencing (NGS). What is NGS? How does it work? Have you heard of Nanopore technologies? In this episode Dr. Jose Alexander and Daniel Navas from Advent Health Orlando, join the podcast to talk about NGS. They brought it to their laboratory and discuss the whole process, including the validation, challenges, and more. This episode was originally published on February 9th, 2024 Guest: Dr. Jose Alexander Daniel Navas Questions? Feedback? Send those to letstalkmicro@outlook.com Want to support the podcast? Here's how: Venmo: https://venmo.com/u/letstalkmicro Buy me a Ko-fi: https://ko-fi.com/letstalkmicro

Drs. Sabari and Yu discuss the molecular landscape of HER2-mutant lung cancer, including its genomic characteristics, common co-mutations, and differences between HER2 mutations and HER2 amplification. This discussion also explores the prevalence and clinical patterns of HER2 mutations, their oncogenic mechanisms, their impact on tumor behavior and metastases, and potential environmental or genetic contributors to their development.

 March 28, 2025 Scott, Mark, and Dr. Ray Painter discuss questions that came into the PRS Helpdesk. NGS sent a newsletter about the use of: cpt code G0463 as a primary code for G2211. Need more info if possible.Do nurse practitioners get paid at 100% for procedures like a PNE when signing notes in NM by themselves?a) Medicare NGS is denying CPT 52332 for bilateral stents with denial CO-151. This seems to be a constant problem with denials for frequency and/or bilateral stents.Has the policy been changed; I have not been able to find any changes regarding stents insertion or exchanges.Thanksb)Hi,Wondering if you can help me with this Medicare patients.NGS is denying the claim on several patients stating that this code has a frequency limit on 52332.NGS has a problem with both frequency and bilateral stentsI have searched everywhere and find no information on this code for frequency limits per year or bilateral stents.Appreciate any help on this code.Free Kidney Stone Coding CalculatorDownload NowPRS Billing and Other Services - Book a Call with Mark Painter or Marianne DescioseClick Here to Get More Information and Request a Quote Join the Urology Pharma and Tech Pioneer GroupEmpowering urology practices to adopt new technology faster by providing clear reimbursement strategies—ensuring the practice gets paid and patients benefit sooner.https://www.prsnetwork.com/joinuptp Click Here to Start Your Free Trial of AUACodingToday.com   The Thriving Urology Practice Facebook group.The Thriving Urology Practice Facebook Group link to join:https://www.facebook.com/groups/ThrivingPractice/ 

Join us for an insightful episode of the Oncology Brothers podcast as we dive deep into the world of renal cell carcinoma (RCC) with Dr. Katy Beckermann, the Medical GU Director of Cancer Research at Tennessee Oncology. In this episode, hosts Drs. Rahul & Rohit Gosain, practicing medical oncologists, discuss the latest advancements in RCC treatment, including: •⁠  ⁠The role of Pembrolizumab in the adjuvant setting based on the Keynote 564 study and its implications for early-stage disease. •⁠  ⁠Current treatment paradigms for metastatic RCC, including dual checkpoint inhibitors, TKI with immunotherapy, and single-agent options. •⁠  ⁠The importance of patient characteristics and IMDC risk categorization in treatment decisions. •⁠  ⁠Insights into sequencing therapies, including the use of Belzutifan for refractory disease and the management of side effects. •⁠  ⁠The role of ctDNA, PD-L1 testing, and NGS in RCC. Whether you're a community oncologist or simply interested in the latest in cancer care, this episode is packed with valuable information to help you stay informed and provide the best care for your patients. YouTube: https://youtu.be/Bbv9N7-YKIM Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and leave a review to let us know how we're doing and how we can continue to support you in the community!  

It could be argued that biology has always boiled down to chemistry, and that chemistry has always boiled down to physics. However, not many would deny that the fields of biology and chemistry are overlapping more than ever, with both leveraging computing methods, also more than ever. This conversation with Dr. Ramesh Jha, Technical Staff Member at Los Alamos National Laboratory (LANL), crosses biology, chemistry, and computing methods. The work of his biome team at LANL uses computational tools to inform the design of enzymes that are produced via PCR-based cloning and then expressed in microbes. They use fluorescent gene circuits in these microbes, along with flow cytometry, to screen these large libraries for advantageous gain-of-function variants. When they find an interesting mutation, they isolate it, sequence it, and produce and evaluate those biocatalytic enzymes for bioremediation, biomanufacturing, and other important applications. Ramesh makes this complex and interdisciplinary science approachable and gives hope to how it could help address problems of “forever chemicals” and other environmental and manufacturing challenges. Join us for this interesting and inspiring conversation.  Subscribe to get future episodes as they drop and if you like what you're hearing we hope you'll share a review or recommend the series to a colleague.  Visit the Invitrogen School of Molecular Biology to access helpful molecular biology resources and educational content, and please share this resource with anyone you know working in molecular biology. For Research Use Only. Not for use in diagnostic procedures.

Join Drs. Rahul & Rohit Gosain in this insightful episode of the Oncology Brothers podcast as they continue their treatment algorithm series, focusing on the rapidly evolving landscape of bladder cancer. They are joined by Dr. Joaquim Bellmunt, a medical oncologist and director of bladder cancer at the Dana-Farber Cancer Institute, who shares his expertise on the latest treatment paradigms for both muscle invasive and non-muscle invasive bladder cancer. In this episode, you'll learn about: •⁠  ⁠The distinction between muscle invasive and non-muscle invasive bladder cancer and their respective treatment approaches. •⁠  ⁠The role of BCG treatment and emerging options for BCG-refractory disease. •⁠  ⁠The significance of the NIAGARA trial and its implications for neoadjuvant chemotherapy and perioperative immunotherapy. •⁠  ⁠Current strategies for managing muscle invasive bladder cancer, including the use of cisplatin-based therapies and the introduction of immunotherapy. •⁠  ⁠Insights into the metastatic space, including the use of enfortumab vedotin (EV) and pembrolizumab, and the importance of next-generation sequencing (NGS) in treatment decisions. •⁠  ⁠Key side effects to monitor with various treatments and the importance of maintaining quality of life for patients. Whether you're a healthcare professional or simply interested in the latest advancements in oncology, this episode is packed with valuable information. YouTube: https://youtu.be/apUp2-BkgWQ Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/   Don't forget to like, share, and subscribe for more discussions on cancer treatment algorithms!  

Lucy Swift from the National Garden Scheme came into our Mix 92.6 studio to share some of the exciting plans for this year's National Garden Scheme (NGS). Lucy told us all about how the NGS raises huge sums for charities and also what's coming up for the NGS in Hertfordshire over the next few weeks. Lucy, who is a gardener by profession, also shared some of her favourite varieties of daffodils now available to us. All in all it was a truly Spring time discussion with the outdoors in mind.

Dr. John Sweetenham and Dr. James Foran discuss the evolving treatment landscape in acute myeloid leukemia, including new targeted therapies, advances in immunotherapy, and the current role for allogeneic transplantation. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. There has been steady progress in the therapies for acute myeloid leukemia (AML) in recent years, largely based on an increasing understanding of the molecular mechanisms which underlie the disease. On today's episode, we'll be discussing the evolving treatment landscape in AML. We'll explore risk group stratification, new targeted therapies, advances in immunotherapy for AML, and also a little about the current role for allogenic transplantation in this disease.  I'm delighted to welcome Dr. James Foran to this discussion. Dr. Foran is a professor of medicine and chair of the Myeloid Malignancies and Blood and Marrow Transplant Disease Group at the Mayo Clinic Comprehensive Cancer Center. He's based in Jacksonville, Florida.  Our full disclosures are available in the transcript of this episode.  James, it's great to have you join us on the podcast today, and thanks so much for being here. Dr. James Foran: I'm delighted and thank you for the invitation. Thank you very much. Dr. John Sweetenham: Sure, James, let's get right into it. So, our understanding of the molecular mechanisms underlying AML has resulted not only in new methods for risk stratification in this disease, which have added refinement to cytogenetics, but also has resulted in the development of many new targeted agents. Understanding that this is a complex area of investigation, and our time is somewhat limited, can you give us a high-level update on the current state of the art in terms of how risk factors are being used for treatment selection now? Dr. James Foran: Absolutely. I think in the past, you know, we had things broken down pretty simply into make a diagnosis based on morphology, do cytogenetics, break patients into the groups of those who were more likely to benefit from therapy – so-called favorable risk – those where the intensive therapies were less likely to work – so-called poor adverse risk, and then this large intermediate group that really had variable outcomes, some better, some worse. And for a long time, the progress was in just identifying new subtle cytogenetic risk groups. And then, late 1990s, we began to understand that FLT3 mutations or NRAS mutations may be more adverse than others that came along. In the first part of this millennium, in the, you know, 2000-2010 range, a lot of work was being done to understand better or worse risk factors with single genes. The ability to do multiplex PCR, and then more recently NGS platforms, have allowed us to really look at many genes and identify many mutations in patients. At the beginning that was used just to sort of refine – who did a little better, who did a little worse with intensive therapy – helped us decide who may benefit more from an allogeneic transplanter for whom that would not be necessary.  But the good news is that really, we're now starting to target those mutations. One of the first molecularly targeted treatments in leukemia was FLT3 mutations, where we knew they were adverse. Then along came targeted treatments. I was involved in some of those early studies looking at sunitinib, sorafenib, more recently midostaurin, now quizartinib, FDA approved, and gilteritinib in the relapse refractory setting.  So we're moving into a state where we're not just refining prognosis, we're identifying targets. You know, it's been slow progress, but definite incremental progress in terms of outcomes by looking for FLT3 mutations, then looking for IDH mutations, and more recently, mutations involving NPM1 or rearrangement of what we used to call the MLL gene, now the lysine methyltransferase 2A or KMT2A rearrangement, where we now have targets. And it's not just for refinement of prognosis, but now we're identifying therapeutic targets for patients and ways to even look for measurable residual disease which is impacting our care. Dr. John Sweetenham: That's great, James. And I'm going to expand on that theme just a little bit and perhaps ask you to elaborate a little bit more on how the introduction of these new therapies have specifically impacted frontline therapy. And a couple of ancillary questions maybe to go along with that: First of all, is ‘7+3' a standard therapy for anybody in 2025? And maybe secondly, you know, could you comment also maybe briefly on older patients with AML and how you think maybe the treatment landscape is changing for them compared with, say, 5 or 10 years ago? Dr. James Foran: I'll start with the therapy and then work my way back. So we've had ‘7+3' cytarabine daunorubicin or cytarabine anthracycline since 1976, and we're still using it as the backbone of our intensive therapy. There is still an important role for it, particularly in younger or fitter patients, and particularly for those with intermediate or favorable risk genetic groups or cytogenetic risk groups just because we achieve high rates of remission. Our 30-day induction mortality rates are lower now than they were 10 and 20 years ago. Our supportive care is better. And we still have a busy inpatient hospital service here at Mayo Florida and my colleagues in Rochester and Arizona as well giving intensive therapy. So that remains the backbone of curative therapy for younger adults. We are trying to be a little more discriminating about who we administer that to. We are trying to add targeted agents. We know from, now, two different randomized trials that the addition of a FLT3 inhibitor, either midostaurin or more recently quizartinib, has a survival advantage in patients with a FLT3 mutation, or for quizartinib, a FLT3/ITD mutation. And so yes, ‘7+3' remains important.  Off protocol for somebody who just comes in with acute leukemia in a 40-year-old or 30-year-old or even early 60s and fit, we would still be considering ‘7+3' therapy and then waiting for an expedited gene mutation panel and an expedited cytogenetics panel to come back to help us discriminate is that a patient for whom we should be giving a FLT3 inhibitor? I think there's a little more nuance about when we do a day 14 bone marrow, do they really matter as much anymore? I still do them. Some of my colleagues find them less important. But we're still giving intensive therapy. We're still giving high-dose ARA-C consolidation for younger patients who achieve complete remission.  In older adults, it's a different story. You know, it was only in the early part of the 2000s – 2004, 2007 range – where we really got buy-in from randomized studies that low-dose therapy was better than no therapy. There was a lot of nihilism before then about therapy for older adults, especially over age 75. We know that low-dose ARA-C is better than nothing. It looked like azacitidine was better than ARA-C or at least equivalent or slightly better. But with the advent of venetoclax it was a game changer. I ran a national randomized study of intensive therapy in AML. It was the last national randomized study of intensive therapy in older patients right before venetoclax got approved. And we were very excited about our results, and we thought we had some really interesting clinical results. And suddenly that's a little bit obsolete in patients over 70 and particularly over age 75 because of the high remission rates with azacytidine venetoclax or hypomethylating agents, so-called HMAs and venetoclax and the survival advantage. Now, it's not a home run for everybody. We quote 60% to 70% remission rates, but it's a little different based on your cytogenetics and your mutation profile. You have to continue on therapy so it's continuous treatment. It's not with curative intent, although there are some people with long-term remission in it. And the median survival went from 10 months to 15 months. So home run? No, but definitely improved remissions, meaningful for patients off transfusions and better survival. So right now it's hard to find an older adult who you wouldn't give azacitidine and venetoclax or something similar, decitabine, for instance, and venetoclax, unless somebody really was moribund or had very poor performance status or some reason not to. And so ‘7+3' is still relevant in younger adults. We're trying to get better results with ‘7+3' by adding targeted agents and azacitine and venetoclax in older adults.  I think the area of controversy, I guess there are two of them, is what to do in that overlap age between 60 and 75. Should people in that age still get intensive therapy, which we've used for years – the VIALE-A trial of aza-venetoclax was age 75 plus – or with cardiac comorbidities? And I think if you're 68 or 72, many of us are starting to bias towards aza-venetoclax as generally being better tolerated, generally being more outpatient, generally being slow and steady way to get a remission. And it doesn't stop you from going to transplant for somebody who might still be a candidate.  The other area of controversy is somebody under 60 who has adverse cytogenetics where we don't do very well with ‘7+3,' we still give it and we might do just as well with decitabine venetoclax. A lot of us feel that there's equipoise in the 60 to 75 group where we really can ask a question of a randomized study. Retrospective studies might suggest that intensive therapy is a little better, but there are now a couple of randomized studies happening saying, “Can we replace ‘7+3' in that intermediate age with aza-venetoclax?” And for younger adults similarly, we're looking to see how we apply that technology. Those are the areas where we're really trying to investigate what's optimal for patients and that's going to require randomized trials. Dr. John Sweetenham: Oh, that's great, thank you. And I'll just extend that question a little bit more, particularly with respect to the new targeted therapies. How much are they impacting the treatment of these patients in the relapse and refractory setting now? Dr. James Foran: Oh, they're definitely impacting it. When I trained and probably when you trained, AML was still a medical emergency. But that was the thing that you admitted to the hospital immediately, you started therapy immediately. The rule was always that's the one thing that brings the fellow and the consultant in at night to see that new patient on a Friday or Saturday. Now, we'll still admit a patient for monitoring, but we try not to start therapy for the first three or five or seven days if they're stable, until we get those genetics and those genomics back, because it helps us discriminate what therapy to pursue. And certainly, with FLT3 mutations, especially FLT3/ITD mutations, we're adding FLT3 inhibitors and we're seeing a survival advantage. Now, on the surface, that survival advantage is in the range of 7% or 10%. But if you then pursue an allogeneic transplant in first remission, you're taking disease where we used to see 30%, 40% long-term survival, maybe less, and you're pushing that to 60%, 70% in some studies. And so we're now taking a disease that– I don't want to get off topic and talk about Ph+ ALL. But that's a disease where we're actually a little excited. We have a target now, and it used to be something really adverse and now we can do a lot for it and a lot about it.  The other mutations, it's a little more subtle. Now, who knew until 2010 that a mutation in a sugar metabolism gene, in isocitrate dehydrogenase, or IDH was going to be so important, or even that it existed. We know that IDH1 and IDH2 mutations are still a minority of AML, certainly less than 10% to 15%, maybe overall. But we're able to target those with specific IDH1 and IDH2 inhibitors. We get single-agent responses. There are now two approved IDH1 inhibitors on the market. We don't yet have the randomized data that adding those to intensive therapy is better, but we're getting a very strong hint that it might be better in older adults who have an IDH mutation, maybe adding those is helpful and maybe adding those to low-intensity therapy is helpful. Those studies are ongoing, and we're also trying with low-intensity treatments to add these agents and get higher remission rates, deeper remissions, longer remissions. I think a lot of work has to be done to delineate the safety of that and the long-term efficacy. But we're getting hints it's better, so I think it is impacting.  The other area it's impacting is when you pick up adverse mutations and those have crept into our classification systems like an ASXL1 mutation or RUNX1 mutation for instance, or some of the secondary AML mutations like BCOR and others, where that's helping us discriminate intermediate-risk patients who we think aren't going to do as well and really helping us select a group who's more likely to get benefit from allogeneic transplant or for whom at least our cure rates without allo transplant are low. And so I think it's impacting a lot. Dr. John Sweetenham: Great. And I'm going to pick up now, if I may, on a couple of things that you've just mentioned and continue the theme of the relapsed and refractory setting. We've started to see some reports which have looked at the role of immune strategies for patients with AML, in particular CAR T or NK cells. Can you comment a little on this and let us know whether you think either these two strategies or other immune strategies are likely to have a significant role in AML in the future? Dr. James Foran: They are, but I think we're still a step behind finding the right target or the right way to do it. If you think of allogeneic transplantation as the definitive immune therapy, and we know for adverse AML we can improve survival rates and cure rates with an allotransplant, then we know inherently that immune therapy matters. And so how do we do what they've done in large cell lymphoma or in CD19 targeting for B cell malignancies? How do we bring that to acute myeloid leukemia? There have been a number of efforts. There have been at least 50 trials looking at different targets. CD33, CD123, CD7, others, CLL-1. So, there have been a number of different trials looking at how to bind a CAR T or a CAR T construct that can be active. And we have hints of efficacy. There was kind of a provocative paper in the New England Journal of Medicine a year ago in April of last year from a Chinese group that looked at a CD7-based CAR T and it was 10 patients, but they used CD7 positive acute leukemia, AML or ALL and had a CD7-targeted CAR T and they actually incorporated that with a haploidentical transplant and they had really high remission rates. People tolerated it quite well. It was provocative. It hasn't yet been reproduced on a larger scale, but the strong hints that the strategy is going to work.  Now, CD33 is a little tricky to have a CAR T when CD33 is expressed on normal hematopoietic cells. CD123 likewise. That's been something where there's, I think, still promise, but we've struggled to find the trials that make that work. Right now, there's a lot of interest in leveraging NK cells and looking, for a couple of reasons, but NK cells are attractive and NK cell markers might be attractive targets. NK cells might have similar degrees of immune efficacy. It's speculative, but they are likely to have less cytokine release syndrome and less neurotoxicity than you see with CAR T. And so it's kind of attractive to leverage that. We have had some ongoing trials looking at it with bispecifics and there certainly are trials looking at it with CAR NK-based strategies. One of the antigens that people looked at is the NK group 2D. NK group 2D or NKG2D is overexpressed in AML and its ligands overexpressed. And so that's a particular potential target. So, John, it's happening and we're looking for the hints of efficacy that could then drive a pivotal trial to get something approved.  One of the other areas is not restricting yourself just to a single antigen. For instance, there is a compound that's looking at a multi-tumor-associated antigen-specific T-cell therapy, looking at multiple antigens in AML that could be overexpressed. And there were some hints of activity and efficacy and actually a new trial looking at a so-called multi-tumor associated antigen-specific T cell therapy. So without getting into specific conflicts of interest or trials, I do think that's an exciting area and an evolving area, but still an investigational area. I'll stop there and say that we're excited about it. A lot of work's going there, but I'm not quite sure which direction the field's going to pivot to there. I think that's going to take us some time to sort out. Dr. John Sweetenham: Yeah, absolutely. But as you say, exciting area and I guess continue to watch this space for now.  So you've mentioned allogeneic stem cell transplants two or three times during this discussion. Recognizing that we don't have an imatinib for AML, which has kind of pushed transplant a long way further back in the treatment algorithm, can you comment a little on, you know, whether you think the role of stem cell transplantation is changing in AML or whether it remains pretty much as it was maybe 10 years ago? Dr. James Foran: By the way, I love that you use imatinib as an introduction because that was 6 TKIs ago, and it tells you the evolution in CML and you know, now we're looking at myristoyl pocket as a target, and so on. That's a great way to sort of show you the evolution of the field.  Allogeneic transplant, it remains a core treatment for AML, and I think we're getting much smarter and much better about learning how to use it. And I'm just going to introduce the topic of measurable residual disease to tell you about that. So I am a little bit of a believer. Part of my job is I support our allogeneic transplant program, although my focus is acute myeloid leukemia, and I've trained in transplant and done it for years and did a transplant fellowship and all that. I'm much more interested in finding people who don't need a transplant than people who do. So I'm sort of looking for where can we move away from it. But it still has a core role. I'll sidestep and tell you there was an MDS trial that looked at intermediate or high-risk MDS and the role of allogeneic transplant that shows that you about double your survival. It was a BMT CTN trial published several years ago that showed you about double your three-year survival if you can find a donor within three months and get to a transplant within six months. And so it just tells you the value of allotransplant and myeloid malignancy in general. In AML we continue to use it for adverse risk disease – TP53 is its own category, I can talk about that separately – but adverse risk AML otherwise, or for patients who don't achieve a really good remission. And I still teach our fellows that an allotransplant decreases your risk of relapse by about 50%. That's still true, but you have to have a group of patients who are at high enough risk of relapse to merit the non-relapse mortality and the chronic graft versus host disease that comes with it. Now, our outcomes with transplant are better because we're better at preventing graft versus host disease with the newer strategies such as post-transplant cyclophosphamide. There are now new FDA-approved drugs for acute and chronic graft versus host disease, ruxolitinib, belumosudil, axatilimab now. So we have better ways of treating it, but we still want to be discriminating about who should get it.  And it's not just a single-minded one-size-fits-all. We learned from the MORPHO study that was published in the JCO last year that if you have FLIT3-positive AML, FLIT3/IDT-positive AML, where we would have said from retrospective studies that your post-transplant survival is 60% give or take, as opposed to 15% or 20% without it, that we can discriminate who should or shouldn't get a transplant. Now that trial was a little bit nuanced because it did not meet its primary endpoint, but it had an embedded randomization based upon MRD status and they used a very sensitive test of measurable residual disease. They used a commercial assay by Invivoscribe that could look at the presence of a FLT3/ITD in the level of 10 to the minus 5th or 10 to the minus 6th. And if you were MRD-negative and you went through a transplant, you didn't seem to get an advantage versus not. That was of maintenance with gilteritinib, I'll just sort of put that on there. But it's telling us more about who should get a transplant and who shouldn't and who should get maintenance after transplant and who shouldn't.  A really compelling study a year ago from I don't know what to call the British group now, we used to call them the MRC and then the NCRI. I'm not quite sure what to call their studies at the moment. But Dr. Jad Othman did a retrospective study a year ago that looked at patients who had NPM1 mutation, the most common mutation AML, and looked to see if you were MRD positive or MRD negative, what the impact of a transplant was. And if you're MRD negative there was not an advantage of a transplant, whereas if you're MRD positive there was. And when they stratified that by having a FLT3 mutation that cracked. If you had a FLT3 mutation at diagnosis but your NPM1 was negative in remission, it was hard to show an advantage of a transplant. So I think we're getting much more discriminating about who should or should not get a transplant by MRD testing for NPM1 and that includes the patients who have a concomitant FLT3 mutation. And we're really trying to learn more and more. Do we really need to be doing transplants in those who are MRD-negative? If you have adverse risk genetics and you're MRD-negative, I'll really need good data to tell me not to do a transplant, but I suspect bit by bit, we'll get that data. And we're looking to see if that's really the case there, too. So measurable residual disease testing is helping us discriminate, but there is still a core role of allogeneic transplant. And to reassure you, compared to, I think your allotransplant days were some time ago if I'm right. Dr. John Sweetenham: Yes. Dr. James Foran: Yeah. Well, compared to when you were doing transplants, they're better now and better for patients now. And we get people through graft versus host disease better, and we prevent it better. Dr. John Sweetenham: That's a great answer, James. Thanks for that. It really does help to put it in context, and I think it also leads us on very nicely into what's going to be my final question for you today and perhaps the trickiest, in a way. I think that everything you've told us today really emphasizes the fact that the complexity of AML treatment has increased, primarily because of an improved understanding of the molecular landscape of the disease. And it's a complicated area now. So do you have any thoughts on what type of clinical environment patients with AML should be evaluated and treated in in 2025? Dr. James Foran: Yeah, I want to give you a kind of a cautious answer to that because, you know, I'm a leukemia doctor. I work at a leukemia center and it's what we focus on. And we really pride ourselves on our outcomes and our diagnostics and our clinical trials and so on. I am very aware that the very best oncologists in America work in private practice and work in community practice or in networks, not necessarily at an academic site. And I also know they have a much harder job than I have. They have to know lung cancer, which is molecularly as complicated now as leukemia, and they have to know about breast cancer and things that I don't even know how to spell anymore. So it's not a question of competence or knowledge. It's a question of infrastructure. I'll also put a little caveat saying that I have been taught by Rich Stone at Dana-Farber, where I did a fellowship a long time ago, and believe Rich is right, that I see different patients than the community oncologists see with AML, they're seeing different people. But with that caveat, I think the first thing is you really want to make sure you've got access to excellence, specialized hematopathology, that you can get expedited cytogenetics and NGS testing results back. There was a new drug, approved just a few months ago, actually, for relapsed AML with a KMT2A rearrangement, revumenib. We didn't talk about the menin inhibitors. I'll mention them in just a second. That's a huge area of expansion and growth for us. But they're not found on NGS platforms. And normal cytogenetics might miss a KMT2A-rearrangement. And we're actually going back to FISH panels, believe it or not, on AML, to try to identify who has a KMT2A-rearrangement. And so you really want to make sure you can access the diagnostic platforms for that.  I think the National Referral Labs do an excellent job. Not always a really fast job, but an excellent job. At my institution, I get NGS results back within three days or four days. We just have an expedited platform. Not everybody has that. So that's the key, is you have to be able to make the diagnosis, trust the pathologist, get expedited results. And then it's the question of trying to access the targeted medications because a lot of them are not carried in hospital on formulary or take time to go through an insurance approval process. So that's its own little headache, getting venetoclax, getting gilteritinib, getting an IDH1 inhibitor in first line, if that's what you're going for. And so I think that requires some infrastructure. We have case managers and nurses who really expedite that and help us with it, but that's a lot of work. The other piece of the puzzle is that we're still with AML in the first month and maybe even the second month. We make everybody worse before we make them better. And you have to have really good blood bank support. I can give an outpatient platelet transfusion or red cell transfusion seven days a week. We're just built for that. That's harder to do if you're in a community hospital and you have to be collaborating with a local blood bank. And that's not always dead easy for somebody in practice. So with those caveats, I do find that my colleagues in community practice do a really good job making the diagnosis, starting people on therapy, asking for help. I think the real thing is to be able to have a regional leukemia center that you can collaborate with, connect with, text, call to make sure that you're finding the right patients who need the next level of diagnostics, clinical trial, transplant consults, to really get the best results.  There was some data at ASH a couple of years ago that looked at – the American Society of Hematology and ASCOs had similar reports – that looked at how do we do in academic centers versus community practice for keeping people on therapy. And on average, people were more likely to get six cycles of therapy instead of three cycles of therapy with azacitidine venetoclax at an academic center. Now, maybe it's different patients and maybe they had different cytogenetics and so on, but I think you have to be patient, I think you have to collaborate. But you can treat those patients in the community as long as you've got the infrastructure in place. And we've learned with virtual medicine, with Zoom and other platforms that we can deliver virtual care more effectively with the pandemic and beyond. So I think we're trying to offer virtual consults or virtual support for patients so they can stay in their home, stay in their community, stay with their oncologists, but still get access to excellent diagnostics and supportive care and transplant consults, and so on. I hope that's a reasonable answer to that question. It's a bit of a nuanced answer, which is, I think there's an important role of a leukemia center, and I think there's a really fundamental role of keeping somebody in the community they live in, and how we collaborate is the key to that. And we've spent a lot of time and effort working with the oncologists in our community to try to accomplish that.  John, I want to say two other things. I didn't mention in the molecular platforms that NPM1 mutations, we can now target those on clinical trials with menin inhibitors. We know that NPM1 signals through the Hoxa9/Meis1 pathway. We know that similar pathways are important in KMT2A rearrangements. We know that there are some other rare leukemias like those with NUP98 rearrangement. We can target those with menin inhibitors. The first menin inhibitor, revuminib, was approved by the FDA for KMT2A. We have others going to the FDA later this year for NPM1. There are now pivotal trials and advanced expanded phase 1/2 studies that are showing 30% response rates. And we're looking to see can we add those into the first-line therapy. So, we're finding more targets.  I'll say one last thing about molecular medicine. I know I'm a little off topic here, but I always told patients that getting AML was kind of like being struck by lightning. It's not something you did. Now, obviously, there are risk factors for AML, smoking or obesity or certain farm environments, or radioactive exposures and so on. But bit by bit, we're starting to learn about who's predisposed to AML genetically. We've identified really just in the last five or eight years that DDX41 mutations can be germline half the time. And you always think germline mutations are going to cause AML in a younger patient, but the median age is 60 to 70 just like other AMLs. They actually might do pretty well once they get AML. We've reported that in several papers. And so we're trying to understand who that has a RUNX1 mutation needs germline testing, who with a DDX41 needs germline testing. And we're trying to actually come up with a cleaner pathway for germline testing in patients to really understand predisposition, to help with donor selection, to help with family counseling. So I think those are other areas where a leukemia center can contribute for somebody in who's community practice to understand genomic or genetic complexity in these patients. And we're starting to develop the databases that support that. Dr. John Sweetenham: Yeah, great. Thanks, James. I loved your answer about the clinical environment too. And I know from a patient-centric perspective that I know that patients would certainly appreciate the fact that we're in a situation now where the folks taking care of them will make every effort to keep them close to home if they possibly can.  I want to thank you, James, for an incredible review of a very complex subject and I think you did a great job. I think we all will have learned a lot. And thanks again for being willing to share your insights with us today on the ASCO Daily News Podcast. Dr. James Foran: John, it's my pleasure. And as you know, I'll do anything for a latte, so no problem at all. Dr. John Sweetenham: Okay. I owe you one, so thank you for that.  And thank you to our listeners for your time today. You'll find links to the studies we've discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. 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. Find out more about today's speakers:  Dr. John Sweetenham  Dr. James Foran Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook  ASCO on LinkedIn  Disclosures:    Dr. John Sweetenham:    No relationships to disclose Dr. James Foran: Stock and Other Ownership Interests: Aurinia Pharmaceuticals Consulting or Advisory Role: Peerview, CTI BioPharma Corp, Remix Therapeutics, Cardinal Health, Medscape, Syndax, Autolus Therapeutics Research Funding (Inst.): Chordia Therapeutics, Abbvie, Actinium Pharmaceuticals, Kura Oncology, Sellas Life Sciences, Novartis, Roivant, Celgene/Bristol-Myers Squibb, Astellas Pharma, SERVIER Travel, Accommodations, Expenses: Peerview

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Toni Choueiri, a leading GU medical oncologist from Dana-Farber Cancer Institute. Together, they dive into the highlights from the GU ASCO 2025 conference, covering key studies and updates in the world of genitourinary oncology. Episode Highlights: •⁠  ⁠TALAPRO-2: An in-depth discussion on the role of PARP inhibitors in prostate cancer, focusing on the study's design, findings, and the importance of germline and NGS testing. •⁠  ⁠NIAGARA Update: Insights into the new standard of care for resectable muscle-invasive bladder cancer and the promising results from the perioperative approach with Durvalumab. •⁠  ⁠CheckMate-9ER Update: A look at the combination of Cabozantinib and Nivolumab in first-line metastatic RCC, including the latest findings and implications for treatment beyond the first line. •⁠  TiNivo2: Exploring the role of Tivozanib in the treatment landscape of RCC and potential sequencing strategies. Join us for this informative discussion that aims to keep community oncologists up to date with the latest advancements in cancer care. If you find this episode helpful, please share it with your colleagues and leave us a review! YouTube: https://youtu.be/OzeHhyAdF9Q Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Don't forget to subscribe for more insights and updates from the Oncology Brothers!

Season 2 of Absolute Gene-ius comes to a close with a look back at the topics and inspiring conversations that have defined the series. From exploring innovative uses of digital PCR to uncovering its synergy with other molecular tools, this season was packed with insights for scientists at all levels.Dive into the details as co-hosts Jordan Ruggieri and Christina Bouwens revisit memorable episodes, including using dPCR as a low-cost precursor to single-cell sequencing and its role in quantifying active mRNA in groundbreaking drug development. Hear from experts like Parker Wilson, Christian Cobaugh, and Raquel Munoz, who share how digital PCR is revolutionizing their workflows and complementing other tools like qPCR and NGS.Of course, it wouldn't be Absolute Gene-ius without a few puns! Stick around for some lighthearted banter as Jordan and Christina celebrate the season's success, share their favorite moments, and hint at what's coming in Season 3. Stay curious, and we'll see you next cycle!Visit the Absolute Gene-ius pageto learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

BUFFALO, NY — February 24, 2025 — A new #researchpaper was #published in Aging (Aging-US) on January 22, 2025, in Volume 17, Issue 1, titled “EpiAge: a next-generation sequencing-based ELOVL2 epigenetic clock for biological age assessment in saliva and blood across health and disease.” The research team, experts from both industry (EpiMedTech Global, HKG Epitherapeutics Ltd) and academic institutions (McGill University, Oxford University, University of Catania, and the Research Institute-IRCCS), led by first author David Cheishvili and corresponding author Moshe Szyf, have developed EpiAgePublic, a new method to estimate biological age using only three key DNA sites in the ELOVL2 gene, a well-known marker of aging. Unlike traditional methods that require analyzing thousands of DNA regions, this approach simplifies the process while maintaining accuracy. Their findings show that EpiAgePublic performs as well as, or even better than, more complex models in predicting biological age in diverse populations. Biological age measures how fast or slow a person's body is aging. It can be different from chronological age and is influenced by genetics, lifestyle, and health conditions. Understanding biological aging can help researchers and clinicians identify age-related diseases like Alzheimer's disease and develop anti-aging treatments. However, many existing biological age tests rely on expensive and complicated processes. The EpiAgePublic model overcomes these challenges with a simple yet powerful approach. The study analyzed data from over 4,600 individuals across different health conditions, including Alzheimer's disease and HIV. It confirmed that EpiAgePublic accurately tracks aging patterns and can identify factors such as chronic illness or stress that accelerate the aging process. Importantly, the researchers demonstrated that the test works well using saliva samples, offering a convenient and non-invasive alternative to blood-based tests. This makes it easier to conduct epigenetic age testing in both clinical and research settings. “The simplicity and precision of epiAgePublic, designed for compatibility with next-generation sequencing (NGS) technologies, mark a significant step forward in the field of epigenetic research.” The ability to measure epigenetic aging with a quick and cost-effective test has significant implications for healthcare, longevity research, and personalized medicine. This method could be used in hospitals, wellness clinics, and longevity studies to track aging and evaluate the effectiveness of anti-aging interventions. It may also help clinicians detect early signs of aging-related diseases, allowing for better preventive care. Finally, the study's findings highlight the advantages of next-generation sequencing in epigenetic research, leading the way for more precise and accessible aging diagnostics. Future research will explore how this model can be expanded to other health conditions and used in routine medical practice. DOI - https://doi.org/10.18632/aging.206188 Corresponding author - Moshe Szyf - moshe.szyf@epimedtech.com Author interview - https://www.youtube.com/watch?v=NA8Vctks0gY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206188 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Topics and terms such as biosafety, biosecurity, containment, and contamination are things most of us have heard of and think about at some level, but with the pace of molecular biology moving faster than ever, these are topics with implications that are reaching farther than ever. We're joined by Dr. Ryan Burnette and Dr. Lauren Richardson from Merrick and company for this episode, and they're ace communicators that help walk us through the expanding horizon and implications of these topics.This conversation starts on the basic topics, like what biocontainment is and what's needed for each of the four levels of biosafety labs, but it quickly moves beyond, shining a light on the security and containment needs for more than just the organisms. We hear about how the data and methods used to do modern molecular biology, as well as the data generated in the experiments, are equally precious and in need of protection and containment. With public health and safety on the line, and an acknowledgement that the pace of science moves faster than that of policy, we get into the idea of who really owns responsibility for protecting data. Your role might be more important than you know, so don't miss this conversation that will make you pause and think! Subscribe to get future episodes as they drop and if you like what you're hearing we hope you'll share a review or recommend the series to a colleague.  Visit the Invitrogen School of Molecular Biology to access helpful molecular biology resources and educational content, and please share this resource with anyone you know working in molecular biology. For Research Use Only. Not for use in diagnostic procedures.

On episode #73 of the Infectious Disease Puscast, Daniel and Sara review the infectious disease literature for the weeks of 1/16/25 – 1/29/25. Hosts: Daniel Griffin and Sara Dong Subscribe (free): Apple Podcasts, RSS, email Become a patron of Puscast! Links for this episode Viral AGA clinical practice guideline on the prevention and treatment of hepatitis B virus reactivation (Gastroenterology) Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients (Nature Communications) Insect-specific RNA viruses detection in Field-Caught Aedes aegypti mosquitoes from Argentina using NGS technology (PLoS Neglected Tropical Diseases) Bacterial Oral regimens for rifampin-resistant, fluoroquinolone-susceptible tuberculosis (NEJM) Impact of antibiotic treatment and predictors for subsequent infections in multidrug-resistant Pseudomonas aeruginosa catheter-associated asymptomatic bacteriuria (American Journal of Infection Control) Identification of the skip phenomenon among patients With Staphylococcus lugdunensis infective endocarditis (OFID) Emergence of infective endocarditis due to Serratia spp. (OFID) Reduction of vancomycin-associated acute kidney injury with montelukast (JID) Fungal The Last of US Season 2 (YouTube) Pulmonary co-infection of Pneumocystis jirovecii and Aspergillus species (OFID) Impact of fluconazoleon outcomes of patients with primary pulmonary coccidioidomycosis (CID) Parasitic Comparative outcomes of Babesiosis in immunocompromised and non-immunocompromised hosts (CID) Miscellaneous Hidradenitis suppurativa (LANCET) A severe case associated with mixed infections of Pasteurella multocida, Bacteroides pyogenes and Fusobacterium necrophorum due to a snow leopard bite (CMI: Clinical Microbiology and Infection) INSIDE-OUT: Introduction of speakers at IDWeek events (OFID) Music is by Ronald Jenkees Information on this podcast should not be considered as medical advice.

Welcome to the Olink® Proteomics in Proximity podcast!  Below are some useful resources mentioned in this episode:  Olink® Reveal, accessible NGS-based proteomics for every lab: https://olink.com/products/olink-revealOlink tools and software·       Olink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/·       Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies   Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm   Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...   Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music: https://music.amazon.com/podcasts/d97...   Podcast Addict: https://podcastaddict.com/podcast/409...   Deezer: https://www.deezer.com/show/5178787   Player FM: https://player.fm/series/series-3396598   In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink technology called the Proximity Extension Assay (PEA). More information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY  For any questions regarding information Olink Proteomics, please email us ...

Obesity is one of the most pressing health challenges of our time, with genetic and molecular factors playing a crucial role in how our bodies regulate weight. In this season opener, we explore the science behind obesity, focusing on how hormones, genetics, and brain circuits influence feeding behavior and body weight. Join us for a fascinating discussion about the interplay between molecular biology and real-world health outcomes.Our guest, Dr. Giles Yeo, is a professor of molecular neuroendocrinology at the University of Cambridge and an expert in the genetics of obesity. With decades of research experience, Dr. Yeo dives into how hormones like GLP-1 interact with the brain and how genetic mutations can affect eating behaviors. He also explains the innovative molecular biology techniques his lab uses to map brain circuits and decode the genetic influences on body weight.But this episode isn't all about the lab. Dr. Yeo shares his journey from studying the genetics of Japanese pufferfish to becoming a leading voice in obesity research and science communication. Whether he's decoding how Ozempic works or reflecting on the importance of good science communication, Dr. Yeo's passion for the field—and his knack for making complex topics relatable—shines through. Subscribe to get future episodes as they drop and if you like what you're hearing we hope you'll share a review or recommend the series to a colleague.  Visit the Invitrogen School of Molecular Biology to access helpful molecular biology resources and educational content, and please share this resource with anyone you know working in molecular biology. For Research Use Only. Not for use in diagnostic procedures.

Welcome back to the Oncology Brothers podcast! In this episode, we dive into the highlights from ASH 2024, focusing on key studies in leukemia. Join hosts Drs. Rahul and Rohit Gosain as they discuss groundbreaking research with Dr. Uma Borate from The Ohio State University. Episode Highlights: •⁠  ⁠KOMET 007 Study: An in-depth look at the Phase 1 study on the Menin inhibitor Ziftomenib, exploring its promising results in frontline settings for patients with NPM1 mutations and KMT2A rearrangements. •⁠  ⁠CPX351 vs. 7+3 Induction: A discussion on the liposomal formulation CPX351 and its effectiveness compared to the traditional 7+3 induction therapy, particularly in patients with myelodysplasia-related AML. •⁠  ⁠Venetoclax Combinations: Insights into the use of Venetoclax in combination with various therapies, including its role in treating patients without actionable mutations. Key Takeaways: •⁠  ⁠The importance of NGS testing in identifying targetable mutations in AML. •⁠  ⁠Promising response rates and manageable toxicities associated with Menin inhibitors. •⁠  ⁠The ongoing debate regarding the best induction therapy for AML patients. Don't miss this informative discussion that sheds light on the evolving landscape of leukemia treatment! Subscribe for more updates on oncology topics, including lymphoma, CLL, and myeloma discussions from ASH 2024. Thanks for tuning in! We are the Oncology Brothers. Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

In this episode of the Oncology Brothers podcast, hosts Drs. Rohit and Rahul Gosain welcome Dr. Pamela Kunz, a world-renowned medical oncologist from the Yale Cancer Center, to discuss the complex landscape of neuroendocrine tumors (NETs). Join us as we explore: •⁠  ⁠The classification of neuroendocrine tumors based on grade, histological features, and the significance of KI-67. •⁠  ⁠The role of imaging modalities, including Gallium PET-CT and its importance in evaluating disease extent. •⁠  ⁠Treatment strategies for localized versus metastatic NETs, including the use of somatostatin analogs and the nuances of observation versus intervention. •⁠  ⁠Insights into the latest treatment options, including lutetium dotatate, Capecitabine-Temozolomide, and the anticipated approval of Cabozantinib. •⁠  ⁠The potential role of NGS testing and the challenges of combining chemotherapy with immunotherapy in high-grade neuroendocrine tumors. Whether you're a healthcare professional or someone interested in the latest advancements in oncology, this episode provides valuable insights into the management of neuroendocrine tumors. Don't forget to like, subscribe, and check out our other episodes for more discussions on current standard of care treatment options, conference highlights, and new drug approvals. We look forward to seeing you at GI ASCO in January 2025! #OncologyBrothers #NeuroendocrineTumors #CancerCare #MedicalOncology #Podcast #NETs Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

Jacob and Trent are joined by special guest Antonio Pitts - winner of the Next Generation Storytellers Scholarship - to discuss the impact NGS has made on his life, how a dream of being a spy peaked his interest in acting and the vision he has for himself in the film industry. --- Support this podcast: https://podcasters.spotify.com/pod/show/jacob-young1/support

In this episode of the Oncology Brothers podcast, hosts Drs. Rahul and Rohit Gosain welcome Dr. Martina Murphy, an Associate Professor of Medicine and Senior Associate Dean of Graduate Medical Education at the University of Florida, to discuss the current landscape of ovarian cancer. Join us as we dive into the critical aspects of diagnosing and managing ovarian cancer, including: •⁠  ⁠The importance of surgical staging and primary debulking surgery •⁠  ⁠The role of genetic testing, including BRCA and NGS, in treatment planning •⁠  ⁠Adjuvant therapy options, focusing on platinum-based chemotherapy and the use of Bevacizumab •⁠  ⁠Insights into PARP inhibitors and their application in BRCA-positive and wild-type patients •⁠  ⁠Navigating treatment options for relapsed and refractory ovarian cancer, including the use of antibody-drug conjugates like Mirvetuximab and Trastuzumab Deruxtecan (TDXd). Dr. Murphy shares her expertise on the latest advancements in ovarian cancer treatment, the significance of genetic testing, and the management of side effects associated with various therapies. Tune in for a comprehensive overview of the standard of care for ovarian cancer and the evolving treatment landscape. Don't forget to check out our other episodes for more discussions on practice-changing data and current treatment options in oncology! Subscribe to the Oncology Brothers podcast for more insights and updates in the field of oncology! Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

Prof. Alessio Di Fonzo shares the results of his award winning, multi-center work examining genetic data from people with early-onset PD in hopes of highlighting the difficulties in interpreting genetic variants emerging from NGS-multigene panels. Read the article.

Same may think of the pathologist's toolbox as only the microscope and their eyes, but in reality today's pathologists are using more and more molecular methods like NGS and PCR in additional to their traditional tools. Meet Parker Wilson, MD, PhD. Parker is a faculty member Perelman School of Medicine at the University of Pennsylvania, focused on using modern molecular tools to investigate chronic kidney disease. He explains his work phenomenally, both from the general aspects, all the way down to the molecular methods, which include digital PCR. We learn about chronic kidney disease and the interesting genetic mutations associated with it, which Parker and his team are finding, include chromosomal loss. For this application, we hear how dPCR is adept at quantifying chromosome ratios within tissues, and is able to help them spot variations of only a single percent or two. Our career corner portion uncovers an academic and career path with uncertainty and challenges one might not expect. Parker helps normalize these challenges and underscores the value of mentors in helping navigate them successfully. In the end, you have a phenomenally intelligent physician scientists sharing his exciting work and his insightful career development advice.Visit the Absolute Gene-ius pageto learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

Dr. Joe Lennerz, Chief Scientific Officer of BostonGene and a pathologist by training, joins Chadi to break down next-generation sequencing (NGS) in simple terms, discussing why some patients undergo NGS while others do not, along with its advantages and limitations. He also explores the impact of NGS on treatment pathways, the practicality of minimal residual disease (MRD) detection, liquid biopsy, and circulating tumor DNA (ctDNA), and whether immediate action should be taken after MRD detection. Additionally, Dr. Lennerz examines multi-cancer early detection technologies, who should be tested, and the future need for regulatory oversight in this rapidly advancing field. Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on YouTube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

Welcome to the Oncology Brothers Podcast! Join Drs. Rahul & Rohit Gosain in this episode as they welcome Dr. Balazs Halmos, a thoracic medical oncologist from Montefiore-Einstein Comprehensive Cancer Center, to discuss the current landscape of metastatic non-small cell lung cancer with actionable mutations in first-line settings. In this informative episode, they cover a wide range of topics including the importance of NGS testing, treatment options for various actionable mutations such as EGFR, ALK, ROS1, RET rearrangements, and more. Dr. Halmos provides valuable insights into decision-making processes, sequencing treatments, and managing toxicities associated with targeted therapies. Don't miss out on this insightful discussion that sheds light on the rapidly evolving space of precision medicine in lung cancer treatment. Stay informed and learn how identifying and targeting specific mutations can optimize treatment outcomes and improve patient quality of life. Tune in to the Oncology Brothers Podcast for expert insights and discussions on the latest developments in oncology. Subscribe now to stay updated on their informative episodes!