EGFR Blockade Reverts Resistance to KRAS^G12C Inhibition in Colorectal Cancer.

ABSTRACT: Most patients with KRAS ^G12C-mutant non-small cell lung cancer (NSCLC) experience clinical benefit from selective KRAS^G12C inhibition, whereas patients with colorectal cancer bearing the same mutation rarely respond. To investigate the cause of the limited efficacy of KRAS^G12C inhibitors in colorectal cancer, we examined the effects of AMG510 in KRAS ^G12C colorectal cancer cell lines. Unlike NSCLC cell lines, KRAS ^G12C colorectal cancer models have high basal receptor tyrosine kinase (RTK) activation and are responsive to growth factor stimulation. In colorectal cancer lines, KRAS^G12C inhibition induces higher phospho-ERK rebound than in NSCLC cells. Although upstream activation of several RTKs interfere

SUBMITTER: Amodio V 

PROVIDER: S-EPMC7416460 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature