Piro Lito, M.D., Ph.D.

Approximately 25 percent of patients with lung cancer harbor mutations in a cancer-causing protein called KRAS. This is the most frequently activated protein found in cancer patients. While precision medicines--which target proteins that are activated less frequently--have revolutionized the care of patients with lung cancer, no such medicines are available to treat patients whose tumors harbor a KRAS mutation. Recent advances have led to the discovery of drugs that target a particular KRAS mutation, KRAS G12C, which is the most common KRAS mutation in patients with lung cancer. Building on our work describing the mechanism of action of these drugs, we will investigate how cancer cells bypass inhibition of KRAS and then identify optimal combination therapies, in order to maximize the effect of these drugs in patients.

Update: KRAS G12C inhibitors are now in phase I clinical trials and promise to be the first effective KRAS oncoprotein directed therapy. We are studying the mechanisms leading to resistance or insensitivity to such treatment. We are determining how cancer cells adapt to therapy and are identifying resistance-causing alterations. We also are identifying effective combination therapies that can be translated to clinical trials with the goal of improving the outcomes of patients with KRAS mutant lung cancer.