KRAS G12C mutant selective inhibitors targeting inactive state have been approved for use in non-small cell lung cancer (NSCLC). Here, using models derived from a patient with NSCLC who progressed on sotorasib (KRAS G12C inhibitor), the authors identify increased KRAS GTP loading as an adaptive resistance mechanism which could be targeted with KRAS G12C inhibitors selective to the GTP active state.
- Marie-Julie Nokin
- Alessia Mira
- Chiara Ambrogio