Testosterone in Androgen Receptor Signaling and DNA Repair: Enemy or Frenemy?

Clin Cancer Res. 2016 Jul 1;22(13):3124-6. doi: 10.1158/1078-0432.CCR-16-0381. Epub 2016 May 10.

Abstract

Androgen suppression mediates transcriptional downregulation of DNA repair genes. Stimulation with supraphysiologic levels of dihydrotestosterone induces formation of lethal DNA breaks through recruitment of topoisomerase II enzymes to fragile DNA sites. Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. Clin Cancer Res; 22(13); 3124-6. ©2016 AACRSee related article by Hedayati et al., p. 3310.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Androgen Receptor Antagonists / therapeutic use*
  • Androgens / therapeutic use
  • Combined Modality Therapy
  • DNA Damage / genetics*
  • DNA Repair / drug effects*
  • DNA Topoisomerases, Type II / metabolism
  • Dihydrotestosterone / therapeutic use*
  • Humans
  • Male
  • Orchiectomy
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Receptors, Androgen / metabolism
  • Signal Transduction
  • Testosterone / antagonists & inhibitors
  • Testosterone / metabolism

Substances

  • Androgen Antagonists
  • Androgen Receptor Antagonists
  • Androgens
  • Poly-ADP-Ribose Binding Proteins
  • Receptors, Androgen
  • Dihydrotestosterone
  • Testosterone
  • DNA Topoisomerases, Type II
  • TOP2B protein, human