The Gut Onc Lab Podcast

In this episode of The GutOnc Lab, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal break down MSI-High GI cancers. A cancer diagnosis is never good news—but this is a setting where tumor biology meaningfully changes what’s possible, with immunotherapy offering real potential for durable responses and even cure.    Key discussion points include: MMR vs. MSI: A diagnostic primer on the difference between IHC (protein) and NGS/PCR (molecular), including how to handle the discordance. The “Parachute” Data: Breaking down the practice-changing CheckMate 8HW results—and why a hazard ratio of 0.21 is hard to ignore. Nick walks through why nivo/ipi is increasingly his frontline default. The COMMIT Curveball: Why the COMMIT trial data didn’t deliver—and what it may tell us about PD-L1 vs PD-1 strategies in colorectal cancer. Pseudoprogression vs Hyperprogression: Tim shares practical, in-the-clinic ways to tell whether a scan is showing immune infiltration… or true disease acceleration. ctDNA at 6 Weeks: How Nick uses early ctDNA dynamics as a real-time readout of response—especially when you’re pushing toward non-operative management. When IO Fails: What next? From CTLA-4 “immune salvage” approaches to where targeted therapy (including BRAF-directed options) fits. Whether you’re screening for Lynch or choosing between single-agent PD-1 and dual checkpoint blockade, this episode covers how we’re actually managing dMMR/MSI-H disease right now.   Chapters: (00:00) MSI High Basics (02:31) MSI vs MMR Methods (05:12) Choosing Tests in Practice (09:59) TMB Pitfalls (12:14) Pivotal Immunotherapy Trials (15:13) CheckMate 8HW Results (21:03) Biomarkers for Ipi Nivo (25:47) PD1 vs PDL1 Debate (31:52) Using ctDNA in Practice (34:42) How Long to Treat   You can find us on X: Gut Onc Lab (@TheGutOncLab) / X

Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal break down the blockbuster press release from Revolution Medicine regarding their Phase 3 trial, RASOLUTE 302. For years, KRAS was the "compact, smooth" molecule that defied targeted therapy, but the era of the molecular glue has officially arrived.               Understanding the Breakthrough: The hosts emphasize the shift from "OFF" inhibitors to "ON" inhibitors. The following visual concept illustrates how these new molecular glues utilize a chaperone to finally lock onto the active state of the KRAS protein.   Chapters: 00:00 Press Release Breakthrough 01:21 Why KRAS Was Undruggable 03:14 Limits of G12C Inhibitors 08:43 Trial Results 13:58 What It Means for Patients 20:30 Oncoderm and Support Team 20:56 Whats Next in Trials   You can find us on X: Gut Onc Lab (@TheGutOncLab) / X

Drs. Hornstein, Brown, and Grewal discuss how Claudin 18.2 has quickly become an important actionable biomarker in upper GI cancers, with zolbetuximab now entering frontline treatment for selected HER2-negative, microsatellite-stable patients. They review the key phase 3 data supporting its use, while emphasizing that the major challenge in practice is managing the significant nausea and vomiting seen early in treatment. The conversation also highlights how biomarker sequencing now shapes therapy selection and how future strategies, including ADCs, CAR T-cell therapy, and immunotherapy combinations, may further expand the role of Claudin 18.2 targeting.

In the second episode of The Gut-Onc Collab, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal tackle the explosive growth of targeted therapies in the Upper GI space. The team dives deep into the "how" and "when" of treating HER2-positive and HER2-negative gastric and gastroesophageal junction (GEJ) adenocarcinomas, moving from perioperative care to the second-line setting.   Key Takeaways: The Matterhorn Trial: Why adding Durvalumab to perioperative FLOT is an immediate practice-changer for resectable gastric/GEJ cancer, and the team’s "oncologist vs. purist" debate on extrapolating this to esophageal patients. Destiny-Gastric 04 (DG04): A look at Trastuzumab Deruxtecan (T-DXd) displacing the long-standing "Ram-Pac" regimen in the second line. The hosts share raw clinical experiences with its toxicity profile and why it is not "Trastuzumab 2.0." Horizon-GEA 01 & Zanidatamab: Analyzing the bispecific antibody that broke the 2-year median OS barrier. The team critiques the trial’s controversial control arm while acknowledging the undeniable "ball don't lie" efficacy data. Clinical Pearls: The necessity of repeat biopsies, the rise of liquid biopsy in monitoring HER2 status, and the "loperamide trick" for managing zanidatamab-induced diarrhea. From precision oncology to "triple-prophylaxis" anti-emetic strategies, this episode provides a roadmap for the modern management of Upper GI malignancies.   Chapters: (00:00) Matterhorn Trial Overview (05:38) Results and Impact (10:29) How Long to Treat (15:25) TDXd vs RamPac Results (16:05) TDXd Toxicity and Dosing (20:28) Liquid Biopsy Questions (21:16) Horizon GEA01 Setup (26:07) Results That Shift Care (32:58) Infusion Reaction Basics (35:17) Closing Reflections  

In this inaugural episode of The Gut Onc Lab, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal sit down to break down the most impactful data from the 2026 ASCO GI Cancers Symposium. From bispecific antibodies in upper GI to the long-awaited "drugging" of KRAS in pancreatic cancer, the team discusses how these latest clinical findings are ready to move from the podium to the clinic.   Key highlights include: Upper GI Advances: A deep dive into the HERIZON-GEA-01 trial and whether the zanidatamab triplet (Zani + Tislelizumab + Chemo) is ready to replace the current standard of care. Claudin 18.2 Synergy: Early signals from the ILUSTRO trial combining zolbetuximab and nivolumab, and the practical challenges of managing infusion toxicities. Pancreatic Cancer Breakthroughs: The "wild" 37% response rate of oral KRAS G12D inhibitors (INCB161734) in heavily pre-treated patients. Whether you are a seasoned practitioner or a trainee, join the collab for a candid look at the "latest and greatest" in GI medical oncology.   Chapters: (00:00) ASCO GI 2026 Kickoff (02:31) HORIZON GEA HER2 Data (04:23) Zanidatamab Practical Takeaways (08:04) Claudin 18.2 Combo Signals (10:13) Managing Zolbetuximab Toxicity (11:45) Pancreatic KRAS G12D Breakthrough (15:26) Breakwater Updates in BRAF CRC (17:58) FOLFOX vs FOLFIRI Debate (20:52) Closing Thoughts and Sign Off