Swarnali Acharyya, PhD

It is estimated that 40% of lung cancer patients with mutated KRAS G12C gene develop brain metastasis. Brain metastasis leads to a significant decline in cognitive and motor function, daily functioning, illness and accelerated death. There are now two FDA-approved KRAS G12C inhibitors that can penetrate the brain and show clinical responses. Nonetheless, despite striking initial responses with these drugs, most patients develop resistance to the drug and often die from metastatic relapses to the brain. The way in which brain metastasis develops in this lung cancer is unknown. We will investigate mechanisms of brain metastasis and explore a new target for drug treatment of this disease. We also aim to determine which patients are at risk of brain metastasis using novel biomarkers, so we can avoid unnecessary overtreatment and toxicities in lung cancer patients. These studies can reveal novel therapeutic strategies for treating brain metastasis and prolonging the survival of cancer patients with KRAS G12C-mutated lung cancer.

Update:

We have made progress in performing all the initial preclinical studies that are serving as proof-of-principle experiments for Year 2. We have developed a new slice assay format which allows multiple drug testing within a short timeframe of 3 days, which is being implemented for KRAS-mutant lung cancers. These studies can reveal novel therapeutic strategies for treating brain metastasis and prolonging the survival of cancer patients with KRASG12C-mutated lung cancer.