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

Trends Cancer. 2020 May;6(5):419-431. doi: 10.1016/j.trecan.2020.01.018. Epub 2020 Feb 26.

Abstract

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.

Keywords: cancer microenvironment; cell death; chemoradiation; dying cell; tumor repopulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Antineoplastic Agents / adverse effects*
  • Cell Death / drug effects
  • Cell Death / immunology*
  • Cell Death / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cell Survival / radiation effects
  • Cellular Senescence / drug effects
  • Cellular Senescence / immunology
  • Cellular Senescence / radiation effects
  • Chemoradiotherapy / adverse effects*
  • Humans
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Signal Transduction / radiation effects
  • Tumor Escape / drug effects
  • Tumor Escape / radiation effects
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Tumor Microenvironment / radiation effects

Substances

  • Antineoplastic Agents
  • Adenosine Triphosphate