S17 Ep20: Biomarker-Directed Therapies Move the GI Oncology Paradigm Beyond a One-Size-Fits-All Approach: With Michael J. Pishvaian, MD, PhD

Biomarker-directed strategies are fundamentally transforming GI oncology, shifting the treatment paradigm from one-size-fits-all approaches to molecularly defined precision medicine. Dr. Pishvaian highlights the necessity of identifying specific genetic alterations—such as MSI-high, NTRK fusions, HER2, CLAUDIN18.2, and BRAF V600E—to optimize therapeutic outcomes. While clinical guidelines increasingly mandate comprehensive testing, practical implementation remains inconsistent, with testing rates often falling below 60%. To address these gaps, clinicians must prioritize early testing, including liquid NGS and ctDNA, to guide frontline decisions and manage resistance. The integration of targeted therapies, such as KRAS inhibitors and combination regimens, offers significant survival benefits but requires rigorous management of toxicities. Ultimately, universal biomarker testing at diagnosis is essential to ensure patients receive the most effective, personalized care, as clinical presentation alone cannot reliably identify these actionable molecular subgroups.