Damon Runyon Researchers

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John R. Ferrarone, MD

Adenocarcinoma is the most common type of lung cancer. Approximately 10% of patients with lung adenocarcinoma will have a tumor that simultaneously carries mutations in genes called KRAS and LKB1. Patients that have a lung cancer harboring both these mutations develop resistance to chemotherapy more rapidly, are more likely to develop brain metastases, and have a worse overall prognosis. Currently, there are no targeted therapies available for patients with this type of lung cancer. Mutations in genes like KRAS and LKB1 lead to a rewiring of normal cellular processes that results in cancer. Importantly, this rewiring also makes tumors more dependent on certain cellular functions. These functions represent cancer-specific vulnerabilities that can be targeted to disrupt tumor growth. In order to identify these vulnerabilities in lung cancers with mutations in both KRAS and LKB1, Dr. Ferrarone is utilizing the CRISPR/Cas9 DNA editing technology on a genome-wide scale. Using CRISPR, he will introduce gene “knockouts” in lung cancer cells carrying both KRAS and LKB1 mutations to see which genetic disruptions are most lethal to the cancer. Identification of the most significant tumor vulnerabilities may lead to the development of new targeted therapies to treat this type of lung cancer.

Project title: "Seeking and evaluating novel therapeutic targets in human lung adenocarcinomas with loss-of-function mutations in LKB1"
Institution: Weill Cornell Medicine
Named Award: Lee Cooperman Physician-Scientist
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Harold E. Varmus, MD
Cancer Type: Lung
Research Area: Cell Biology