Paneth-Like Transition Drives Resistance to Dual Targeting of KRAS and EGFR in Colorectal Cancer

Using genetically engineered mouse models, patient-derived organoids and xenografts, as well as clinical specimens, scientists discovered that colorectal tumors surviving combined KRAS and EGFR inhibition acquire a Paneth-like cell state—a secretory lineage typically confined to the intestinal crypt.