Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer

Trends Endocrinol Metab. 2010 May;21(5):315-24. doi: 10.1016/j.tem.2010.01.002. Epub 2010 Feb 6.


Prostate cancer remains a leading cause of cancer death, as there are no durable means to treat advanced disease. Treatment of non-organ-confined prostate cancer hinges on its androgen dependence. First-line therapeutic strategies suppress androgen receptor (AR) activity, via androgen ablation and direct AR antagonists, whereas initially effective, incurable, 'castration-resistant' tumors arise as a result of resurgent AR activity. Alterations of AR and/or associated regulatory networks are known to restore receptor activity and support resultant therapy-resistant tumor progression. However, recent evidence also reveals an unexpected contribution of the AR ligand, indicating that alterations in pathways controlling androgen synthesis support castration-resistant AR activity. In this report, the mechanisms underlying the lethal pairing of AR deregulation and aberrant androgen synthesis in prostate cancer progression will be discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Androgen Antagonists / therapeutic use
  • Androgens / biosynthesis*
  • Castration
  • Humans
  • Male
  • Prostate / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / physiology*


  • AR protein, human
  • Androgen Antagonists
  • Androgens
  • Receptors, Androgen