Sharks Journal Club

4/4 Take-home message. Daraxonrasib showed meaningful activity across common KRAS variants including G12D, G12V and G12R. The key lesson: High efficacy comes at the cost of frequent dose optimisation rather than discontinuation. Now all eyes on RASolute-302. 🔬

New #NEJM publication on daraxonrasib (RMC-6236) in previously treated RAS-mutated PDAC. Let’s break down the study: patient population, efficacy, toxicity and key take-home messages. 🧵⬇️ @NEJM #PDAC #KRAS #Oncology #PrecisionOncology

CholangiocarcinomaDay: CCA is no longer “rare”. Precision oncology is no longer “future”. Late diagnosis should no longer be “acceptable”. 2026 Consensus is clear: early detection, molecular profiling, and faster access to targeted therapies. Let’s make it happen. @atuvibi

The real question: Can we build a simple IHC panel (GATA6 ± basal markers) to define PDAC biology and stratify patients in future trials, instead of treating all PDAC the same?

GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer O’Kane et al. | Clinical Cancer Research Can GATA6 reliably separate basal-like vs classical PDAC as defined by the Moffitt transcriptomic classifier?

Open questions: • Will tumor biology and the TME help guide targeted and combination therapies in the future? • Does the TME, not fully explored in PASS-01, play a key role in treatment response?

PASS-01 ( Jennifer J. Knox et al. JCO, 2025) Study purpose: To evaluate whether molecular or clinical biomarkers can inform first-line treatment selection between FFX and GnP in de novo metastatic PDAC.

🟢 Vesicular → enterochromaffin cell, neuroendocrine identity → best OS 🟡 Epithelial → Enteroendocrine cell, epithelial differentiation → favorable OS 🔵 Immune → inflammatory → intermediate OS 🔴 Mesenchymal → Absence hormone expression, stromal activation (CAFs)

TODAY 8/01/2026 Molecular portrait of small intestinal NET (Nature, 2025) This study identifies 4 molecular subtypes of small intestinal NETs. Redefining prognosis beyond anatomy and grade.