The current landscape of using direct inhibitors to target KRAS^G12C-mutated NSCLC.

ABSTRACT: Mutation in KRAS protooncogene represents one of the most common genetic alterations in NSCLC and has posed a great therapeutic challenge over the past ~ 40 years since its discovery. However, the pioneer work from Shokat's lab in 2013 has led to a recent wave of direct KRAS^G12C inhibitors that utilize the switch II pocket identified. Notably, two of the inhibitors have recently received US FDA approval for their use in the treatment of KRAS^G12C mutant NSCLC. Despite this success, there remains the challenge of combating the resistance that cell lines, xenografts, and patients have exhibited while treated with KRAS^G12C inhibitors. This review discusses the varying mechanisms of resistance that limit long-lasting effective treatment of those direct inhibitor

SUBMITTER: Batrash F 

PROVIDER: S-EPMC10625227 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature