TEAD Inhibitors Sensitize KRAS^G12C Inhibitors via Dual Cell Cycle Arrest in KRAS^G12C-Mutant NSCLC.

ABSTRACT: KRAS^G12C is one of the most common mutations detected in non-small cell lung cancer (NSCLC) patients, and it is a marker of poor prognosis. The first FDA-approved KRAS^G12C inhibitors, sotorasib and adagrasib, have been an enormous breakthrough for patients with KRAS^G12C mutant NSCLC; however, resistance to therapy is emerging. The transcriptional coactivators YAP1/TAZ and the family of transcription factors TEAD1-4 are the downstream effectors of the Hippo pathway and regulate essential cellular processes such as cell proliferation and cell survival. YAP1/TAZ-TEAD activity has further been implicated as a mechanism of resistance to targeted therapies. Here, we investigate the effect of combining TEAD inhibitors with KRAS^G12C inhibitors in KRAS

SUBMITTER: Tammaccaro SL 

PROVIDER: S-EPMC10142471 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature