Cellular senescence in premalignant lesions and cancer

Cellular senescence, which is a terminal cell cycle arrest, is a potent tumor suppressor mechanism that limits cancer initiation and progression; it also limits tissue damage response. While senescence is protective in the cell autonomous manner, senescent cells secrete a variety of factors that lead to inflammation, tissue destruction and promote tumorigenesis and metastasis in the sites of their presence. Therefore we study the effects of the presence of senescent cells on tumorigenesis using complex mouse models.  In order to regulate the presence of the senescent cells we study the mechanisms of interaction of senescent cells with NK cells and other immune cells, and harness these mechanisms for elimination of senescent cells. We also evaluate the impact of components of the main pathways regulating cell viability, apoptosis and autophagy for their specific contribution to the viability of senescent cells. The ability to eliminate senescent cells will lead to novel ways of cancer prevention and treatment, by elimination of senescent cells from the sights of tissue damage, premalignant lesions and tumors following therapy.