Abstract
Androgen receptor (AR)-mediated signaling is critical to the growth and survival of prostate cancer. Although medical castration and antiandrogen therapy can decrease AR activity and lower PSA, castration resistance eventually develops. Recent work exploring the molecular structure and evolution of AR in response to hormonal therapies has revealed novel mechanisms of progression of castration-resistant prostate cancer and yielded new targets for drug development. This review focuses on understanding the mechanisms of persistent AR signaling in the castrate environment, and highlights new therapies either currently available or in clinical trials, including androgen synthesis inhibitors and novel direct AR inhibitors.
Copyright © 2012 Elsevier Inc. All rights reserved.
MeSH terms
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Androgen Antagonists / pharmacology*
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Androgen Antagonists / therapeutic use
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Androstadienes / pharmacology
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Androstadienes / therapeutic use
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Benzamides
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Benzimidazoles / pharmacology
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Benzimidazoles / therapeutic use
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Humans
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Imidazoles / pharmacology
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Imidazoles / therapeutic use
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Male
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Naphthalenes / pharmacology
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Naphthalenes / therapeutic use
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Nitriles
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Phenylthiohydantoin / analogs & derivatives
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Phenylthiohydantoin / pharmacology
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Phenylthiohydantoin / therapeutic use
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / physiopathology
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Receptors, Androgen / drug effects*
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Receptors, Androgen / physiology
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Steroid 17-alpha-Hydroxylase / drug effects
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Testosterone / metabolism
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Thiohydantoins / pharmacology
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Thiohydantoins / therapeutic use
Substances
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Androgen Antagonists
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Androstadienes
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Antineoplastic Agents
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Benzamides
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Benzimidazoles
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Imidazoles
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Naphthalenes
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Nitriles
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Receptors, Androgen
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Thiohydantoins
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apalutamide
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Phenylthiohydantoin
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Testosterone
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enzalutamide
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Steroid 17-alpha-Hydroxylase
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orteronel
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3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene