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.

Automated summary

Cellular senescence is a stress response associated with aging and disease, including cancer, and plays a complex role in tumor progression and therapy resistance. Senescent cells undergo a stable cell cycle arrest and secrete bioactive molecules known as the senescence-associated secretory phenotype (SASP). While induction of senescence in preneoplastic cells can limit cancer initiation, senescent cells in the tumor microenvironment (TME) can promote tumor progression, metastasis, and therapy resistance. Senotherapies, including senolytic drugs that eliminate senescent cells, have emerged as a potential strategy to impede tumor progression by restoring anti-tumor immune responses and influencing the TME.