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Lancet Oncol. 2009 Oct;10(10):981-91. doi: 10.1016/S1470-2045(09)70229-3.

Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target.

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  • 1Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Abstract

Activation of the androgen receptor is crucial for prostate cancer growth at all points of the illness. Current therapies targeting the androgen receptor, including androgen-depletion approaches and anti-androgens, do not completely inhibit the receptor activity. Prostate cancer cells develop resistance to castration by acquiring changes that include androgen-receptor overexpression and overexpression of enzymes involved in androgen biosynthesis, which result in reactivation of the receptor. Based on an understanding of these resistance mechanisms and androgen biosynthesis pathways, new anti-androgens and androgen-depleting agents have been developed. Notably, promising activity has been shown in early phase trials by MDV3100, a new anti-androgen designed for activity in prostate cancer model systems with overexpressed androgen receptor, and by abiraterone acetate, a CYP17A inhibitor that blocks steroid biosynthesis in the adrenal gland and possibly within the tumour. Both agents are undergoing phase 3 testing. Here, we review the basic science and clinical development of these and other agents.

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PMID:
19796750
[PubMed - indexed for MEDLINE]
PMCID:
PMC2935850
Free PMC Article

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