Therapy-induced senescence in cancer: from detection to intervention

Therapy-induced senescence (TIS) has emerged as an important contributor to treatment resistance and poor prognosis in clinical cancer therapy. Senescence initially acts as a tumor-suppressive mechanism by enforcing stable cell-cycle arrest, while the senescence-associated secretory phenotype (SASP) promotes the formation of pro-tumorigenic microenvironment, ultimately leading to therapeutic resistance and tumor relapse. Precise detection and targeted elimination of TIS have emerged as an important focus in cancer treatment. In this review, we first summarize tumor-specific fluorescent probes for senescence detection, including enzyme-responsive, non-enzymatic, dual-responsive, and theranostic platforms. We further discuss current senolytic approaches, including classical Bcl-2 family inhibitors, dasatinib-quercetin combinations, and emerging senolytic strategies. In addition, we summarize the cutting-edge senolytic regimens that synergize with chemotherapy, radiotherapy, photothermal therapy, and immunotherapy. Finally, we highlight the key challenges and future perspectives for clinical translation and application.