DNA double-strand break repair inhibitors as cancer therapeutics

Chem Biol. 2015 Jan 22;22(1):17-29. doi: 10.1016/j.chembiol.2014.11.013. Epub 2015 Jan 8.


Among DNA damages, double-strand breaks (DSBs) are one of the most harmful lesions to a cell. Failure in DSB repair could lead to genomic instability and cancer. Homologous recombination (HR) and nonhomologous end joining (NHEJ) are major DSB repair pathways in higher eukaryotes. It is known that expression of DSB repair genes is altered in various cancers. Activation of DSB repair genes is one of the reasons for chemo- and radioresistance. Therefore, targeting DSB repair is an attractive strategy to eliminate cancer. Besides, therapeutic agents introduce breaks in the genome as an intermediate. Therefore, blocking the residual repair using inhibitors can potentiate the efficacy of cancer treatment. In this review, we discuss the importance of targeting DSB repair pathways for the treatment of cancer. Recent advances in the development of DSB repair inhibitors and their clinical relevance are also addressed.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • DNA Repair* / drug effects
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Recombinases / antagonists & inhibitors
  • Recombinases / metabolism
  • Recombination, Genetic / drug effects
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Recombinases
  • Tumor Suppressor Proteins