Senolytics for Cancer Therapy: Is All that Glitters Really Gold?

SIMPLE SUMMARY: Senescence is an essential component of tumor cell biology and is a primary cell stress response to therapy. While the long-term impact of senescence in cancer therapy is not yet fully understood, the use of senolytics, drugs that selectively kill senescent cells, is an area of active investigation in cancer treatment. Several challenges and unanswered questions have arisen from the current preclinical literature, indicating the need to re-evaluate some of the basic premises and experimental approaches, as well as the potential utility for translating to the clinic the application of senolytics as adjuvants to current cancer therapy. ABSTRACT: Senolytics represent a group of mechanistically diverse drugs that can eliminate senescent cells, both in tumors and in several aging-related pathologies. Consequently, senolytic use has been proposed as a potential adjuvant approach to improve the response to senescence-inducing conventional and targeted cancer therapies. Despite the unequivocal promise of senolytics, issues of universality, selectivity, resistance, and toxicity remain to be further clarified. In this review, we attempt to summarize and analyze the current preclinical literature involving the use of senolytics in senescent tumor cell models, and to propose tenable solutions and future directions to improve the understanding and use of this novel class of drugs.