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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) is generally the initial treatment for men with metastatic prostate cancer. Standard approaches include bilateral orchiectomy or medical orchiectomy using a gonadotropin releasing hormone (GnRH) agonist either 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 castrate-resistant prostate cancer. Contemporary research in men with castrate-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 castrate resistant prostate cancer. These approaches are discussed here.

An overview of the management of advanced prostate cancer is presented separately. (See "Overview of the treatment of disseminated prostate cancer".)

MOLECULAR PATHWAYS

Rationale — Contemporary research has demonstrated that androgen-based pathways continue to have a clinically significant role in the progression of castrate-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 2016. | This topic last updated: Wed Jul 27 00:00:00 GMT 2016.
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