A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer

We show that inhibition of oncogenic KRAS in preclinical models of advanced mCRC exerts a limited benefit, primarily due to the reversion of tumor cells to a stem cell-like state. Our findings highlight the context-dependent effects of oncogenic KRAS mutations and underscore cell plasticity as a therapeutic opportunity. See related commentary by Eng and Yilmaz et al., p. 201.