Cellular senescence: A novel mechanism of therapeutic resistance in prostate cancer.

Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality. Despite the efficacy of androgen deprivation therapy (ADT), patients with advanced PCa eventually progress to a lethal castration-resistant disease state. Cellular senescence represents a stable growth arrest induced by stress signaling cascades or cancer therapeutics, and escape from a senescent state may be implicated in the development of castration resistance. We discuss the mechanisms promoting cellular senescence in PCa and its contribution to therapeutic resistance to ADT, PARP inhibitors, chemotherapy, and radiation. We also summarize the potential of senolytic and senomorphic therapies in targeting senescent prostate cancer cells in the setting of therapy-induced senescence.