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Castration-resistant prostate cancer: Treatments targeting the androgen pathway

Authors
Nancy A Dawson, MD
Charles J Ryan, MD
Section Editors
Nicholas Vogelzang, MD
Jerome P Richie, MD, FACS
W Robert Lee, MD, MS, MEd
Deputy Editor
Michael E Ross, MD

INTRODUCTION

Androgen deprivation therapy (ADT), either alone or in combination with chemotherapy, is generally the initial treatment for men with metastatic prostate cancer. Standard approaches to ADT include bilateral orchiectomy or medical orchiectomy using a gonadotropin releasing hormone (GnRH) agonist, which may be given alone or in combination with an antiandrogen (combined androgen blockade). (See "Initial systemic therapy for castration-sensitive prostate cancer".)

Despite initial response rates of 80 to 90 percent, nearly all men eventually develop progressive disease following ADT; this is referred to as castration-resistant prostate cancer. Contemporary research in men with castration-resistant prostate cancer has led to the development of multiple agents that improved overall survival in phase III trials (table 1).

Insights into the mechanisms by which androgens stimulate growth of prostate cancer cells is leading to the development of new treatments with clinically significant activity in men with castration-resistant prostate cancer. These approaches are discussed here.

Overviews of the management of advanced castration-sensitive and castration-resistant prostate cancer are presented separately. (See "Overview of the treatment of disseminated castration-sensitive prostate cancer" and "Overview of the treatment of castration-resistant prostate cancer (CRPC)".)

MOLECULAR PATHWAYS

Rationale — Contemporary research has demonstrated that androgen-based pathways have a clinically significant role in the progression of castration-resistant prostate cancer. In addition to androgen production by the adrenal gland and testis, several of the enzymes involved in the synthesis of testosterone and dihydrotestosterone, including cytochrome P450 17-alpha-hydroxysteroid dehydrogenase (CYP17), are highly expressed in tumor tissue [1].

                     
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Literature review current through: Nov 2017. | This topic last updated: Sep 05, 2017.
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