Therapy-Induced Senescence in Cancer: From Mechanisms of Tumor Suppression to Translational Exploitation

Cellular senescence is a stable state of cell cycle arrest triggered by diverse stressors, including chemotherapy, radiotherapy, and targeted agents. Therapy-induced senescence (TIS) was initially framed as a beneficial tumor-suppressive outcome, halting the proliferation of damaged cancer cells. However, growing evidence reveals a more complex picture: senescent tumor cells secrete a range of bioactive factors collectively termed the senescence-associated secretory phenotype (SASP), which can remodel the tumor microenvironment, promote immune clearance of senescent cells, but also paradoxically support tumor relapse, therapy resistance, and secondary malignancies under certain conditions. Understanding the dual, context-dependent role of TIS is therefore critical for optimizing cancer treatment strategies, and has spurred substantial interest in pharmacologically modulating senescent cells—either eliminating them (senolytics) or suppressing their harmful secretory output (senomorphics)—as adjuncts to conventional cancer therapy.Therapy-induced senescence occupies a paradoxical position in cancer biology: it can act as a potent tumor-suppressive mechanism, yet senescent cells and their secretory output can also drive relapse, resistance, and secondary malignancy under certain conditions. This duality has created uncertainty around how and when to therapeutically exploit senescence, and has slowed translation of senotherapeutics into clinical practice. The goal of this Research Topic is to consolidate current mechanistic understanding of therapy-induced senescence with translational and pharmacological research, in order to clarify the conditions under which senescence benefits versus harms treatment outcomes. We aim to highlight actionable strategies—including senolytic and senomorphic agents, rational combination regimens, and biomarker-driven patient stratification—that can help resolve this duality in clinical settings. By bringing together mechanistic, preclinical, and clinical contributions in one collection, we hope to provide researchers and clinicians with a clearer framework for integrating senescence biology into cancer treatment design, ultimately accelerating the development of safer and more effective senescence-targeting therapies.This Research Topic welcomes contributions addressing the dual role of therapy-induced senescence in cancer, spanning molecular mechanisms of senescence induction, SASP regulation, immunosurveillance of senescent cells, and pathways linking senescence to tumor relapse, dormancy escape, and therapy resistance. We also invite work on senolytic and senomorphic drug discovery, mechanism-of-action studies, combination regimens with conventional chemotherapy or radiotherapy, and biomarkers for detecting senescence in preclinical and clinical settings. Submissions addressing cancer type–specific or treatment-modality–specific senescence responses, computational/systems-level senescence signature analysis, and long-term risks of senescence induction (e.g., secondary malignancy) are also encouraged.Both preclinical and clinical studies are welcome, as are papers presenting negative or contradictory findings that clarify the context-dependent effects of therapy-induced senescence. Topic editors: Nirmalya Dasgupta, Shanshan Yin Source: https://www.frontiersin.org/research-topics/85516/therapy-induced-senescence-in-cancer-from-mechanisms-of-tumor-suppression-to-translational-exploitation