Dark Side of Cytotoxic Therapy: Chemoradiation-Induced Cell Death and Tumor Repopulation

Accelerated tumor repopulation following chemoradiation is often observed in the clinic, but the underlying mechanisms remain unclear. In recent years, dying cells caused by chemoradiation have attracted much attention, and they may manifest diverse forms of cell death and release complex factors and thus orchestrate tumor repopulation cascades. Dying cells potentiate the survival of residual living tumor cells, remodel the tumor microenvironment, boost cell proliferation, and accelerate cancer cell metastasis. Moreover, dying cells also mediate the side effects of chemoradiation. These findings suggest more caution when weighing the benefits of cytotoxic therapy and the need to accordingly develop new strategies for cancer treatment.