A Critical Appraisal of the Utility of Targeting Therapy-induced Senescence for Cancer Treatment

Cancer chemotherapy and radiotherapy are rarely successful in eliminating the entire tumor population, often leaving behind a subpopulation of senescent cells that can contribute to disease recurrence. These senescent tumor cells also secrete various chemokines and cytokines that may be tumor-promoting and immunosuppressive. Recognition of the deleterious impact of therapy-induced senescence has led to the preclinical development of senolytic compounds that eliminate senescent cells, representing a potential strategy to enhance the efficacy of conventional and targeted anticancer therapy. However, it remains uncertain whether this strategy can or will be translated to the clinic. This review provides a summary of the recent preclinical literature supporting the use of senolytics as an adjunct for cancer treatment, discusses the limitations associated with current preclinical models, and provides perspectives on the clinical development of senolytics in cancer treatment regimens. Overall, preclinical studies support the potential of senolytics to enhance efficacy and prolong the antitumor activity of current standard-of-care cancer therapies that promote senescence. However, further work is needed to develop optimal senolytic agents with the appropriate combination of properties for clinical testing, specifically activity in the context of therapy-induced senescence with acceptable tolerability.