The identification of the genetic mutations responsible for the formation of cancers has paved the way for the development of new drugs which specifically attack cancer cells, resulting in significant improvement in patient outcome. However, tumor development also involves a series of non-genetic mechanisms that allow cancer cells to adapt to their environment and escape therapies. For instance, the regulations of cellular metabolism and protein synthesis appear to be central mechanisms allowing adaptation and reprogramming of cancer cells during tumor development. In this project, we propose to study the mechanisms underlying the reprogramming of cellular metabolism by protein synthesis in the context of lung cancer. Lung cancer is the leading cause of cancer death worldwide and therefore represents a major health concern. Moreover, lung tumors are very heterogeneous and characterized by a multitude of genetic alterations, which renders them resistant to current chemo-, radio- and immunotherapies. Thus, the long-term goal of the proposed project is to characterize the molecular mechanisms that link mRNA translation to the regulation of cancer metabolism in order to identify molecular targets and metabolic vulnerabilities which can be used for the development of new effective treatments. To achieve this goal, we will generate and characterize novel preclinical models of lung cancer. Results obtained from these models will then be validated using human patient material. Ultimately, by deeply characterizing clinically relevant models of lung cancer, this project will provide a better understanding of the complex regulatory mechanisms that support lung cancer development and progression, and will highlight new therapeutic strategies for the treatment of lung cancer.
