title: Testosterone in Androgen Receptor Signaling and DNA Repair: Enemy or Frenemy?
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.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Melvin Lee Kiang
authors.initials: ML
authors.lastname: Chua
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Rob.bristow@rmp.uhn.on.ca.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D013196:Dihydrotestosterone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009919:Orchiectomy; D000075223:Poly-ADP-Ribose Binding Proteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000075223:Poly-ADP-Ribose Binding Proteins; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D004250:DNA Topoisomerases, Type II; C000618814:TOP2B protein, human