Androgen hypersensitivity in prostate cancer: Molecular perspectives on androgen deprivation therapy strategies

Androgen deprivation therapy is initially successful in treating advanced prostate cancer. However, after a period of time tumors inevitably recur. Improved understanding of the various biochemical causes of resistance to hormonal therapy is of crucial importance for developing more effective therap...

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Bibliographic Details
Published in:The Prostate 2011-04, Vol.71 (5), p.550-557
Main Authors: Foley, Ruth, Marignol, Laure, Keane, John P., Lynch, Thomas H., Hollywood, Donal
Format: Article
Language:English
Subjects:
Androgen Antagonists - pharmacology
Androgen Antagonists - therapeutic use
Androgens - pharmacology
Animals
Biological and medical sciences
biomarkers
Dose-Response Relationship, Drug
Gynecology. Andrology. Obstetrics
Humans
Hypersensitivity, Delayed - chemically induced
intermittent androgen withdrawal
Male
Male genital diseases
Medical sciences
Mice
Neoplasms, Hormone-Dependent - drug therapy
Nephrology. Urinary tract diseases
proliferation
Prostatic Neoplasms - drug therapy
testosterone replacement
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
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Summary:Androgen deprivation therapy is initially successful in treating advanced prostate cancer. However, after a period of time tumors inevitably recur. Improved understanding of the various biochemical causes of resistance to hormonal therapy is of crucial importance for developing more effective therapeutic strategies in this cohort of patients. This review discusses the preclinical evidence for androgen hypersensitivity (AH), as a mechanism by which tumors become hormone‐refractory (HR). We propose that the growth of some such tumors may be not only stimulated by, but also dependent on low hormone levels, and furthermore, that normal hormone concentrations can have an inhibitory effect on growth. The incidence and importance of AH merits further investigation both in preclinical studies and during clinical trials of intermittent androgen withdrawal or testosterone replacement. We suggest that a subset of HR prostate cancer patients who have androgen‐hypersensitive tumors could be particularly amenable to these treatments. Finally, potential approaches for developing biomarkers to identify such patients are explored. Prostate 77:550–557, 2011. © 2010 Wiley‐Liss, Inc.
ISSN:0270-4137
1097-0045
DOI:10.1002/pros.21266