Despite recent progress, the role of cell senescence in controlling carcinogenesis remains largely misunderstood, particularly the question of its causal or protective role in tumorigenesis. This difficulty is primarily related to our inability to accurately characterize, track, quantify, purify and remove senescent cells from normal and pathological tissues. Our project, using these new approaches, aims to evaluate the role of senescence in tumor initiation and progression as well as in the response to treatment of lung cancer. We will use a unique knock-in reporter-ablator
mouse model to allow the identification and selective elimination of senescent lung cells and thus define the role of these cells in Kras-induced lung tumorigenesis. We will further combine this research in mice with a detailed analysis of senescence in primary human lung tumors. The role played by senescent cells on the prognosis of different types of lung cancer in humans will be evaluated through the histological analysis of tumors from several cohorts of patients included in already completed clinical trials. Overall, our analysis should provide access to new diagnostic and prognostic tools for lung cancer, develop new biomarkers of different stages of development and be able to define new therapeutic approaches.