Cellular senescence is a stress response associated with aging and disease, including cancer.
Senescent cells undergo a stable cell cycle arrest, change in morphology, 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.