Edward Cooper Stites, M.D., Ph.D.

Institution: The Salk Institute for Biological Studies

Project: Targeted Inhibition of Mutant and Wild-type RAS in KRAS G12C Lung Cancer

Grant(s): Lung Cancer Discovery Award

When the KRAS gene is mutated, it can cause normal cells to become cancerous. Approximately one-third of lung cancer patients have a mutation in the KRAS gene, and patients with such a mutation have a worse prognosis than those who do not. The most common KRAS mutation is known as “KRAS G12C.” A major new discovery in lung cancer treatment is the development of drugs that specifically target KRAS G12C. These drugs are now in clinical trials. Although there is great promise for these agents, it is widely expected that these drugs will need to be combined with other anti-cancer drugs to offer maximal benefit. Our study combines computational methods with traditional experimental approaches to investigate our hypothesis that targeting non-mutant RAS proteins along with KRAS G12C mutants will be an achievable and useful treatment strategy.

Update:

One of the most exciting developments in lung cancer treatment is the development of drugs that specifically target the cancer causing KRAS G12C mutation responsible for many lung cancers. We have previously established a unique approach that combines computational and experimental methods that have proven useful for studying cancer causing KRAS mutations, and our project applies these methods to KRAS G12C lung cancer and its response to these new drugs. We are using our approach to identify which combinations of drugs would be most effective, to elucidate the mechanisms of a promising combination, and to extend our computational tool for broad usage by us and other lung cancer researchers.

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