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Going off the grid: ERα breast cancer beyond estradiol

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Title: Going off the grid: ERα breast cancer beyond estradiol
Authors: Perone, Y
Magnani, L
Item Type: Journal Article
Abstract: Novel studies have linked cholesterol biosynthesis to drug resistance in luminal breast cancer. Structural data suggest that cholesterol metabolites, including 27-hydroxycholesterol (27HC), can act as ERα ligands in these cells. Additionally, hypercholesterolemia has now been linked to breast cancer progression. The focus of this review is to briefly summarize these recent findings and discuss how epigenetic reprogramming is definitively connected to endogenous cholesterol biosynthesis. We elaborate on how these data support a working model in which cholesterol biosynthesis promotes autocrine, pro-invasive signaling via activation of a series of closely related transcription factors. Importantly, we discuss how this mechanism of resistance is specifically associated with aromatase inhibitors. Finally, we examine how the field is now considering the development of anticholesterol therapeutics and companion biomarkers to stratify and treat ERα breast cancer patients. In particular, we review recent progress in pharmaceutical strategies targeting the cholesterol molecular machinery in primary and secondary breast cancers.
Issue Date: 1-Jul-2016
Date of Acceptance: 4-May-2016
URI: http://hdl.handle.net/10044/1/33104
DOI: https://dx.doi.org/10.1530/JME-16-0062
ISSN: 1479-6813
Publisher: BioScientifica
Start Page: F1
End Page: F5
Journal / Book Title: Journal of Molecular Endocrinology
Volume: 57
Copyright Statement: Disclaimer: this is not the definitive version of record of this article. This manuscript has been accepted for publication in Journal of Molecular Endocrinology, 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 available at http://dx.doi.org/10.1530/JME-16-0062
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: A20886
Keywords: Endocrinology & Metabolism
1103 Clinical Sciences
1114 Paediatrics And Reproductive Medicine
0707 Veterinary Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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