Molecular basis for the antiandrogen withdrawal syndrome.
In patients with prostate cancer who manifest disease progression during combined androgen blockade therapy, discontinuation of antiandrogen treatment might result in prostate-specific antigen decline, often associated with clinical improvement. The response called antiandrogen withdrawal syndrome is thus acknowledged as a general phenomenon. However, molecular mechanisms responsible for this syndrome are not completely understood. This article outlines the proposed mechanisms, including alterations of androgen receptor gene and its coregulatory proteins and activation of the signal transduction pathway, and the potential therapeutic approaches based on the specific mechanisms.
Miyamoto
Hiroshi
H
George Whipple Laboratory for Cancer Research, Department of Pathology, and the Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
Rahman
Mujib M
MM
Chang
Chawnshang
C
D000726:Androgen Antagonists / Q000627:therapeutic use*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism; D013375:Substance Withdrawal Syndrome; D016896:Treatment Outcome
D000726:Androgen Antagonists; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen