Targeting the androgen receptor in prostate cancer.

Abstract

INTRODUCTION:

The androgen receptor (AR) is a ligand-activated transcription factor that is expressed in primary and metastatic prostate cancers. There are advances in endocrine therapy for prostate cancer that are based on improved understanding of AR function.

AREAS COVERED:

PubMed has been used to include most important publications on targeting the AR in prostate cancer. AR expression may be downregulated by agents used for chemoprevention of prostate cancer or, in models of advanced prostate cancer, by antisense oligonucleotides. New drugs that inhibit the steroidogenic enzyme CYP17A1 (abiraterone acetate) or diminish nuclear translocation of the AR (enzalutamide) have been shown to improve patients' survival in prostate cancer. However, it is clear that there is a development of resistance to these novel therapies. They may include increased expression of truncated, constitutively active AR or activation of the signaling pathway of signal transducers and activators of transcription.

EXPERT OPINION:

Although introduction of novel drugs have improved patients' survival, there is a need to investigate the mechanisms of resistance further. The role of truncated AR and compensatory activation of signaling pathways as well as the development of scientifically justified combination therapies seems to be issues of a high priority.

• Authors: Zoran Culig
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 15 Issue 10 Pg. 1427-37 (Jul 2014) ISSN: 1744-7666 [Electronic] England
• PMID: 24890318 (Publication Type: Journal Article, Review)

Chemical References

• 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one
• AR protein, human
• Androgen Antagonists
• Anilides
• Antibodies, Neutralizing
• Anticarcinogenic Agents
• Antineoplastic Agents
• Benzamides
• HSP90 Heat-Shock Proteins
• Histone Deacetylase Inhibitors
• Nitriles
• Oligonucleotides, Antisense
• Receptors, Androgen
• Tosyl Compounds
• Phenylthiohydantoin
• hydroxyflutamide
• Flutamide
• enzalutamide
• bicalutamide
• CYP17A1 protein, human
• Steroid 17-alpha-Hydroxylase
• Curcumin

Topics

• Androgen Antagonists (therapeutic use)
• Anilides (therapeutic use)
• Antibodies, Neutralizing (therapeutic use)
• Anticarcinogenic Agents (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Benzamides
• Cell Line, Tumor
• Curcumin (analogs & derivatives, therapeutic use)
• Flutamide (analogs & derivatives, therapeutic use)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Histone Deacetylase Inhibitors (therapeutic use)
• Humans
• Male
• Molecular Targeted Therapy
• Nitriles (therapeutic use)
• Oligonucleotides, Antisense (therapeutic use)
• Phenylthiohydantoin (analogs & derivatives, therapeutic use)
• Phosphatidylinositol 3-Kinases (metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• Receptors, Androgen (metabolism)
• Signal Transduction
• Steroid 17-alpha-Hydroxylase (antagonists & inhibitors)
• Tosyl Compounds (therapeutic use)