Senescence in cancer development and anti-cancer therapy

Cellular senescence, which is a terminal cell cycle arrest, is a potent tumor suppressor mechanism that limits cancer initiation and progression. 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. We 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. We have shown that elimination of senescent cells from premalignant pancreas blocks the development of pancreatic ductal adenocarcinoma (Kolodkin-Gal, Roitman, Ovadya, et al, Gut, 2022).

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.

Prof. Krizhanovsky lecture on the topic: