The androgen/androgen receptor axis in prostate cancer.
OBJECTIVE
The review highlights recently discovered mechanisms that sustain castration-resistant prostate cancer (CRPC) growth and describes advances in CRPC therapeutics.


RESULTS
Recent reports have shed new light on the molecular processes underlying CRPC survival during androgen deprivation therapy (ADT). This study summarizes recent findings and comments on their clinical relevance. Included in this review is a discussion on molecular mechanisms that regulate androgen receptor (AR) signaling in normal prostate epithelium and CRPC, biologically significant differences in the androgen-regulated transcriptional programs of androgen-dependent prostate cancer and CRPC, and recent discoveries involving de-novo androgen production and transport. We review the status and results of current clinical trials and finally, discuss the implications of evidence suggesting a declining importance of AR signaling in prostate cancers with PTEN loss.


CONCLUSIONS
Advances in the understanding of AR signaling in CRPC have identified novel drug targets and improved the rational design of targeted therapy, while illuminating a subset of prostate cancers that may progress to become completely independent of the AR signaling program.
Fred Hutchinson Cancer Research Center and School of Medicine, University of Washington, Seattle, Washington 91809, USA.
Eric G
EG
Bluemn
Peter S
PS
Nelson
D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002369:Castration; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D051059:PTEN Phosphohydrolase; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human