Therapy induced senescence and its implications in cancer

Abstract

Senescence is a phenomenon of ‘end of cells replicative capacity’, characterized by irreversible cell cycle arrest which in the context of cancer, will contain the growth of tumour. Hence possibility of using pro-senescence therapies for cancer therapeutics has generated substantial interest. In this regards there are several reports showing that senescence can be induced in cancer cells by genotoxic agents used in anti-neoplastic therapy, such senescence is called ‘therapy induced senescence’ (TIS). Therapy induced senescent cells undergo cell death or eventual immune-mediated clearance. However, recent reports also show the existence of ‘therapy induced senescence reversal’ mechanisms in some cancers, wherein after a definite period of time, senescent cells overcome the arrest and re-enter the cell cycle, eventually repopulating the tumour which will limit the use of senescence for cancer therapeutics. The data also highlighs that TIS is complex and we do not fully understand many aspects of this phenomenon. Therefore to harness senescence for cancer therapeutics, a deeper understanding of the underlying molecular mechanisms governing establishment and reversal of senescence is required. In the current review, we have discussed current knowledge of the therapeutic agents inducing senescence, their mechanism of induction and the implication of senescence reversal in cancers.