Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies.

Cellular senescence is a stress response associated with aging and disease, including cancer. Senescent cells undergo a stable cell cycle arrest, undergo a change in morphology and metabolic reprogramming, and produce a bioactive secretome termed the senescence-associated secretory phenotype (SASP). In cancer, senescence is an important barrier to tumor progression. Induction of senescence in preneoplastic cells limits cancer initiation, and many cancer therapies act in part by inducing senescence in cancer cells. Paradoxically, senescent cells lingering in the tumor microenvironment (TME) can contribute to tumor progression, metastasis, and therapy resistance. In this review, we discuss the different types of senescent cells present in the TME and how these senescent cells and their SASP reshape the TME, affect immune responses, and influence cancer progression. Furthermore, we will highlight the importance of senotherapies, including senolytic drugs that eliminate senescent cells and impede tumor progression and metastasis by restoring anti-tumor immune responses and influencing the TME. [Display omitted] Senescence can affect cancer cells and different components of the tumor microenvironment (TME). In this review, D'Ambrosio and Gil describe the anti- and pro-tumorigenic roles of senescent cells inside the TME and discuss different therapeutic approaches to kill senescent cells to benefit cancer patients. [ABSTRACT FROM AUTHOR]