Overcoming Adaptive Resistance to KRAS Inhibitors Through Vertical Pathway Targeting

Abstract

KRAS G12C inhibitors have shown promise in KRAS G12C-mutant lung cancer but intrinsic and acquired resistance are common. Cotreatment with inhibitors of the protein phosphatase SHP2 can abrogate the adaptive response of cancer cells to KRAS inhibitors resulting in greater suppression of MAPK signaling and enhanced tumor growth inhibition.See related article by Ryan et al., p. 1633.