Inhibition of ULK1/2 and KRAS^G12C controls tumor growth in preclinical models of lung cancer.

ABSTRACT: Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRAS^G12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRAS^G12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRAS^G12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRAS^G12C signaling increases autophagy in KRAS^G12C-expressing lung cancer cells. Moreover, the combination

SUBMITTER: Ghazi PC 

PROVIDER: S-EPMC11364435 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature