Examining LKB1 status as a biomarker for response of lung cancer to metformin

There is recent evidence that metformin, a drug commonly used to treat diabetes, has anticancer effects and can significantly improve the rate of pathological response in breast cancers treated with chemotherapy. We propose to review clinical records of lung cancer patients treated over the past 25 years at Johns Hopkins to determine whether metformin treatment is associated with improved clinical response to chemotherapy for lung cancer. Because our preliminary laboratory work suggests that lung cancer cells with mutations of the LKB1 gene are particularly sensitive to metformin, we will secondarily determine whether mutations of the LKB1 gene (which is mutated in up to 40% of lung adenocarcinomas) are associated with a higher frequency of response to chemotherapy among these patients treated with metformin. In a second specific aim, we will conduct studies using xenografts of human lung cancers in the laboratory to further examine possible links between LKB1 mutations and response to metformin, with or without paclitaxel. Establishing such a link could lead to improved chemotherapy (using metformin in combination with conventional chemotherapy drugs) and to development of a biomarker that can identify patients with cancers who might have improved response to chemotherapy with metformin.