Cellular senescence in cancer treatment: friend or foe?

Abstract

Damage to DNA, the prime target of anticancer therapy, triggers programmed cellular responses. In addition to apoptosis, therapy-mediated premature senescence has been identified as another drug-responsive program that impacts the outcome of cancer therapy. Here, we discuss whether induction of senescence is a beneficial or, rather, a detrimental consequence of the therapeutic intervention.

Figure 1

Drug-inducible senescence: friend or foe? In response to DNA-damaging agents, cancer cells can rapidly undergo apoptosis or may enter premature senescence as a potential back-up mechanism. Whether cells re-enter the cycle or execute apoptosis out of drug-mediated senescence remains unclear. A terminal arrest of the entire cancer cell population, possibly augmented through increased immunogenicity of senescent cells, is beneficial for the host. In contrast, feeder-like growth that reflects paracrine activity of senescent cells on their non-senescent neighbors, or escape from senescence based on acquired or preexisting mutations, is considered a detrimental outcome.