314P Let’s bring back old drugs to conquer resistance to KRAS G12C inhibitors in NSCLC

Abstract

Once considered undruggable, mutant KRAS has recently emerged as a promising target for anticancer therapies. KRASG12C is the most common mutant isoform in NSCLCs, accounting for 41–49% of cases with G12 substitutions. In KRAS-mutant lung adenocarcinomas that have received previous anticancer therapies, treatment with a selective KRAS G12C inhibitor (sotorasib) causes partial responses in around 38 % of patients. Despite the significant therapeutic responses associated with KRAS inhibitors, their efficacy in patients has been short-lived due to the emergence of drug resistance.