Androgen Receptor Antagonists in the Treatment of Prostate Cancer
Takashi Kawahara and Hiroshi MiyamotoAffiliation:
James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.
AbstractAntiandrogens that block androgen action through the androgen receptor, often in conjunction with chemical or surgical castration, have been widely used for the treatment of advanced prostate cancer. Although this treatment produces a significant clinical response in most of the patients, the majority of the responders eventually develop recurrences termed castration-resistant prostate cancer. In addition, clinically available androgen receptor antagonists have been shown to possess agonist activity, resulting in an increase in serum prostate-specific antigen levels, which is known as the antiandrogen withdrawal syndrome. Recent studies have demonstrated that new types of androgen receptor signaling inhibitors improve survival in men with castration-resistant prostate cancer. Moreover, other drugs may have the potential of not inducing androgen withdrawal response. This article reviews the characteristics of classical and recent androgen receptor antagonists as well as their clinical efficacy in prostate cancer patients. Novel experimental compounds that may more specifically and effectively target androgens and/or androgen receptor signals in hormone-naive and possibly castration- resistant prostate cancer cells are also discussed.
Androgen, androgen receptor, antiandrogen, castration, combined androgen blockade, cytochrome P450-17, hormonal therapy, prostate cancer.
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