Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer.
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.
Kimmel Cancer Center, Department of Cancer Biology and Department of Urology, Thomas Jefferson University, Philadelphia, PA 19107, USA. karen.knudsen@kimmelcancercenter.org
Karen E
KE
Knudsen
Trevor M
TM
Penning
D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000096:biosynthesis*; D002369:Castration; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology*
C410798:AR protein, human; D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen