Direct GDP-KRAS^G12C inhibitors and mechanisms of resistance: the tip of the iceberg.

ABSTRACT: Kirsten rat sarcoma viral oncogene homolog mutations are observed in 25% of lung adenocarcinoma and 40% of these are G12C mutations. Historically, no approved targeted agents were available for patients with any KRAS mutation, and response rates to standard-of-care therapies were suboptimal. Newly developed inhibitors directed toward KRAS^G12C have been successful in clinical trials with overall response rates ranging between 32% and 46%, and two FDA approvals were granted in May 2021 and December 2022 as second-line or later monotherapies. However, rapid tumor resistance complicates their use as a monotherapy. With the rapid development of this novel class of inhibitors, it is important to discern the different types of tumor resistance that may arise and how each can dif

SUBMITTER: Rosen JC 

PROVIDER: S-EPMC10026147 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature