327-Paneth Plasticity in KRAS Colorectal Cancer
The paper investigates the molecular basis for acquired therapeutic resistance in KRAS-mutant colorectal cancer (CRC) following dual inhibition of KRAS and EGFR. The research establishes that CRC cells utilize lineage plasticity, adopting a secretory Paneth-like cell state to survive the targeted therapy. Mechanistically, this adaptive transition is orchestrated by the SMAD1-FGFR3 signaling axis, which drives resistance by allowing the crucial MAPK pathway to reactivate within the surviving Paneth-like cell population. Through extensive preclinical models and analysis of human patient…
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