Senotherapeutics in Cancer

Senotherapeutics represents a cutting-edge paradigm in oncology, focusing on the modulation or elimination of senescent cells to counteract their dual role in cancer—both as tumor suppressors and promoters. This chapter explores the biological underpinnings of cellular senescence, emphasizing its complex involvement in cancer initiation, progression, and therapy resistance. Senotherapeutics is mainly classified into two main types: senolytics, which selectively induce apoptosis in senescent cells; and senomorphics, which suppress the harmful senescence-associated secretory phenotype (SASP) without killing the cells. A detailed mechanistic overview of agents like navitoclax, dasatinib + quercetin, FOXO4-DRI, rapamycin, and metformin is provided, alongside discussions on their impact on the tumor microenvironment (TME), immune modulation, and therapy-induced senescence (TIS). The chapter further examines the synergistic potential of combining senotherapeutics with conventional cancer therapies such as chemotherapy and radiotherapy to prevent recurrence and enhance treatment efficacy. Challenges such as drug specificity, biomarker identification, long-term safety, and public perception are critically analyzed. The chapter concludes with insights into future directions, including advances in drug delivery, immune-mediated senolysis, and the expansion of clinical trials. Overall, this chapter provides a comprehensive and translational perspective on how senotherapy could redefine cancer treatment by targeting the root contributors to tumor progression and relapse.