Uncovering Therapeutic Specificity for Defined Oncogenic KRAS

Cancer growth is driven by mutations in genes called oncogenes. One of the most important oncogenes in lung cancer is KRAS, and this gene is mutated in one third of lung adenocarcinomas. Mutations in KRAS are different in different people but what this means for cancer growth and response to drugs not known. Mouse models uniquely enable lung cancer initiation, growth, and therapeutic treatment in vivo, but current systems are too difficult to generate to uncover the importance of these different KRAS mutations. We have used the cutting-edge technology of CRISPR/Cas9 genome editing to create mouse models of lung cancer in which different tumors are driven by different mutant forms of KRAS. We will use this innovative system to test whether tumors with certain KRAS mutations can be selectively killed by certain drugs. Our proposal will uncover new areas of biology, motivate clinical trials, and facilitate personalized cancer therapy for lung cancer patients with KRAS-mutant tumors.