Targeting KRAS G12C mutation in lung adenocarcinoma

Lung cancer continues to be a major cause of cancer related death globally. Therapies targeting driver mutations have significantly extended the survival of patients whose lung cancer cells harbor these mutations. Patients with KRAS mutations, however, lacked specific targeted therapy until the recent FDA approval of sotorasib, a specific inhibitor of KRAS G12C mutant protein. We will discuss the efficacy and toxicities of the novel KRAS G12C inhibitors as well as other indirect strategies for targeting oncogenic KRAS mutations. We will review the limited literature on acquired resistance to these inhibitors and the novel combinatorial treatment strategies that are being tested currently in clinical trials.