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.
Knudsen
Karen E
KE
Kimmel Cancer Center, Department of Cancer Biology and Department of Urology, Thomas Jefferson University, Philadelphia, PA 19107, USA. karen.knudsen@kimmelcancercenter.org
Penning
Trevor M
TM
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