Enhancing radiosensitivity: Targeting the DNA repair pathways

Timothy J. Jorgensen

Research output: Contribution to journalReview article

Abstract

Radiotherapy is very effective in local control of cancerous tumors, but its curative potential is often limited by intrinsic radioresistance of the tumor cells. Since DNA repair pathways remove radiation-induced DNA lesions and protect cells from lethality, these pathways represent potential therapeutic targets to radiosensitize tumors. In order to achieve a therapeutic gain, however, there must be a differential between tumor and normal cells that can be exploited to preferentially target the DNA repair of the tumor, while sparing surrounding normal tissues, and this has represented a significant challenge to progress. Nevertheless, recent advances in our understanding of DNA repair mechanisms and tumor biology, on both the biochemical and genetic levels, have identified molecular differentials that may increase tumor specificity. This mechanistic insight suggests new strategies for radiotherapeutic targeting of DNA repair. Some of these strategies are reviewed here, including synthetic lethal, replicative stress, cell cycle and hypoxia-based approaches. The example of PARP1 inhibitor use in BRCA1 and 2 mutated breast cancer therapy is discussed, and future directions and challenges are explored.

Original languageEnglish (US)
Pages (from-to)665-670
Number of pages6
JournalCancer Biology and Therapy
Volume8
Issue number8
DOIs
StatePublished - Apr 15 2009

Keywords

  • Cancer
  • DNA repair
  • Hypoxic
  • Poly(ADP-ribose) polymerase
  • Radiation biology
  • Radiotherapy
  • Synthetic lethal

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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