Relevanz der AMP-aktivierten Proteinkinase als Biomarker in der Therapie des nicht-kleinzelligen Lungenkarzinoms

Abstract

Background: It is known for a long time, that there is an association between Diabetes mellitus and cancer diseases. Metformin as widely used antidiabetic drug could possibly have a protective effect on the development of cancer and furthermore it could be effective in therapeutic regimens. We evaluated the influence of metfomin on the AMP-activated protein kinase in non-small cell lung cancer xenografts. We examined if there is a supportive effect of metformin on the response on the monoclonal EGFR antibody Cetuximab in non-small cell lung cancer. Methods: Xenografts with non-small cell lung cancer were treated with cetuximab and metformin followed by measurement of the tumor growth. Afterwards AMPK and p70 S6k expression were determined via western blot on protein level and via rt-PCR on m-RNA level in the tumor probes. Furthermore patient data were analyzed and correlated with the tumor behavior in the xenografts. Results: Starting from 89 surgical NSCLC specimens, which were obtained from primarily diagnosed patients with early-stage tumors, 25 transplantable xenografts were established. There was no influence of metformin on tumor growth. Also there couldn`t be seen any regulation of AMPK or p70S6K in the tumors. We couldn`t show any correlation between tumor doubling time in xenografts and the overall survival, disease free survival or age of the patients. Summary: Patient derived Xenografts allow performing complex pre-clinical studies in non small cell lung cancer. Metformin didn’t influence tumor growth, the tumor response on cetuximab or regulation of AMP activated protein kinase so it doesn’t seem to have any relevance in treatment of non-small cell lung cancer.