Hedgehog signalling is involved in acquired resistance to KRAS^G12C inhibitors in lung cancer cells.

ABSTRACT: Although KRAS^G12C inhibitors have shown promising activity in lung adenocarcinomas harbouring KRAS^G12C, acquired resistance to these therapies eventually occurs in most patients. Re-expression of KRAS is thought to be one of the main causes of acquired resistance. However, the mechanism through which cancer cells re-express KRAS is not fully understood. Here, we report that the Hedgehog signal is induced by KRAS^G12C inhibitors and mediates KRAS re-expression in cancer cells treated with a KRAS^G12C inhibitor. Further, KRAS^G12C inhibitors induced the formation of primary cilia and activated the Hedgehog-GLI-1 pathway. GLI-1 binds to the KRAS promoter region, enhancing KRAS promoter activity and KRAS expression. Inhibition of GLI using si

SUBMITTER: Lee C 

PROVIDER: S-EPMC10789740 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature