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New roles for nuclear receptors in prostate cancer

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Title: New roles for nuclear receptors in prostate cancer
Authors: Leach, DA
Powell, SM
Bevan, C
Item Type: Journal Article
Abstract: Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease - hence the quest for new effective therapies for "castrate-resistant" prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC. The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This reviews aims to provide a snapshot of current knowledge of the roles of different nuclear receptors in prostate cancer, a rapidly-evolving field of research.
Issue Date: 19-Sep-2016
Date of Acceptance: 19-Sep-2016
URI: http://hdl.handle.net/10044/1/41154
DOI: https://dx.doi.org/10.1530/ERC-16-0319
ISSN: 1479-6821
Publisher: BioScientifica
Start Page: T85
End Page: T108
Journal / Book Title: Endocrine-Related Cancer
Volume: 23
Issue: 11
Copyright Statement: © 2016 Society for Endocrinology. Disclaimer: this is not the definitive version of record of this article.This manuscript has been accepted for publication in Endocrine-Related Cancer, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at https://dx.doi.org/10.1530/ERC-16-0319 2016
Sponsor/Funder: Prostate Cancer UK
The Urology Foundation
Funder's Grant Number: PG14-038 / PO 19329
N/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Endocrinology & Metabolism
androgen receptor
endocrine therapy resistance
estrogen receptor
gene transcription
prostate
coactivator
corepressor
LIVER-X-RECEPTOR
LIGAND-BINDING DOMAIN
PROLIFERATOR-ACTIVATED RECEPTORS
LENGTH ANDROGEN RECEPTOR
RECURRENCE-FREE SURVIVAL
XENOGRAFT TUMOR-GROWTH
ALPHA-LINOLENIC ACID
PEROXISOME PROLIFERATOR
PROGESTERONE-RECEPTOR
VITAMIN-D
Oncology & Carcinogenesis
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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