Multifacet Roles of Cellular Senescence in Cancer: Mechanisms and Therapeutic Implications

ABSTRACT Cellular senescence plays a complex, dual role in cancer. Senescent cells induce tumor suppression through cell cycle arrest and immune response activation but also secrete pro‐inflammatory factors via the senescence‐associated secretory phenotype (SASP), which can foster tumor growth, metastasis, and immune evasion. However, the therapeutic potential of targeting senescence mechanisms remains underexplored. This review examines the dual functions of senescent cells in cancer, emphasizing the paradoxical role of the SASP in both promoting tumor progression and modulating immune responses. We explore how SASP factors contribute to tumor growth, metastasis, and immune evasion by reshaping the tumor microenvironment. We then discuss emerging strategies aimed at targeting senescent cells, focusing on approaches for their selective clearance and the modulation of SASP components. These strategies have the potential to enhance the effectiveness of conventional cancer therapies, such as chemotherapy and radiation, by reducing immune‐suppression and improving immune surveillance. Additionally, we delve into the growing interest in SASP‐targeted immunotherapies, which aim to overcome the immunosuppressive effects of senescent cells and boost antitumor immunity. This review emphasizes the importance of targeting senescence and SASP for developing precision‐based cancer therapies, offering new opportunities for next‐generation immunotherapy.