Senotherapies: A novel strategy for synergistic anti-tumor therapy

•Prolonged presence of senescent tumor cells may induce tumorigenesis, metastasis and recurrence.•Senescence escape is the accomplices of treatment failure.•Polyploid may be the cellular morphology of senescence escape.•Senotherapies can improve the efficiency and alleviate the side effects of anti-tumor therapy. Cellular senescence was initially considered an effective antitumor mechanism, and senescence-induced therapy has previously been regarded as an efficient treatment. However, increasing studies have discovered that persistent senescent cells (SNCs) might have unanticipated negative repercussions for antitumor treatment. The long-term build-up of SNCs exacerbates toxic side effects, treatment resistance, and poor prognosis, and tumor cells that undergo senescence escape can acquire stemness to repopulate the tumor, leading to cancer recurrence. Thus, senotherapies that eliminate SNCs could be used as a new strategy for synergistic antitumor therapy. In this review, we summarize the adverse effects of SNCs in tumor development and the mechanisms by which senescent tumor cells escape senescence, discuss the relationship between senescence and polyploidy, and highlight the potential of senotherapies as an emerging adjuvant antitumor treatment strategy. Such a strategy is expected to provide new approaches for antitumor drug development from the perspective of cellular senescence.