The DNA damage response: implications for tumor responses to radiation and chemotherapy

Annu Rev Med. 2015;66:129-43. doi: 10.1146/annurev-med-081313-121208. Epub 2014 Nov 24.

Abstract

Cellular responses to DNA damage are important determinants of both cancer development and cancer outcome following radiation therapy and chemotherapy. Identification of molecular pathways governing DNA damage signaling and DNA repair in response to different types of DNA lesions allows for a better understanding of the effects of radiation and chemotherapy on normal and tumor cells. Although dysregulation of the DNA damage response (DDR) is associated with predisposition to cancer development, it can also result in hypersensitivity or resistance of tumors to therapy and can be exploited for improvement of cancer treatment. We highlight the DDR pathways that are activated after treatment with radiation and different classes of chemotherapeutic drugs and describe mechanisms determining tumor sensitivity and resistance to these agents. Further, we discuss approaches to enhance tumor sensitivity to radiation and chemotherapy by modulating the DDR with a goal of enhancing the effectiveness of cancer therapies.

Keywords: DNA repair; cancer resistance; chemosensitization; radiosensitization; synthetic lethality.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • DNA Damage / drug effects
  • DNA Damage / genetics*
  • DNA Damage / radiation effects
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • DNA Methylation / radiation effects
  • DNA Repair / drug effects
  • DNA Repair / genetics*
  • DNA Repair / radiation effects
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • Radiotherapy*

Substances

  • Antineoplastic Agents