The Power Behind the Throne: Senescence and the Hallmarks of Cancer

Abstract

Cellular senescence is a state of stable proliferative arrest triggered by various stimuli, including oncogenic and other cellular stress. Senescent cells are highly metabolically active and have diverse and profound nonautonomous effects through the senescence-associated secretory phenotype (SASP). It has become increasingly evident that senescent cells can have tumour suppressive or pro-oncogenic effects on adjacent cancer cells and other players in the tumor microenvironment such as the stroma, vasculature, and immune system. Thus, the last decade or so has witnessed a huge leap forward in our understanding of the biology of senescence, promoting it from an autonomous tumor suppressor to a complex, dynamic, and interactive phenotype. It is perhaps not a coincidence that the concept of the “hallmarks of cancer” has also evolved during this period, with the latest iteration ( Hanahan & Weinberg 2011 ) focusing more on the microenvironment. Here, we suggest that cellular senescence could underpin the biology of many of the hallmarks of cancer, making it the true power behind the throne.