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Type: Journal article
Title: Pushing estrogen receptor around in breast cancer
Author: Lim, E.
Tarulli, G.
Portman, N.
Hickey, T.
Tilley, W.
Palmieri, C.
Citation: Endocrine-Related Cancer, 2016; 23(12):T227-T241
Publisher: Bioscientifica Ltd.
Issue Date: 2016
ISSN: 1351-0088
Statement of
Elgene Lim, Gerard Tarulli, Neil Portman, Theresa E Hickey, Wayne D Tilley and Carlo Palmieri
Abstract: The estrogen receptor-α (herein called ER) is a nuclear sex steroid receptor (SSR) that is expressed in approximately 75% of breast cancers. Therapies that modulate ER action have substantially improved the survival of patients with ER-positive breast cancer, but resistance to treatment still remains a major clinical problem. Treating resistant breast cancer requires co-targeting of ER and alternate signalling pathways that contribute to resistance to improve the efficacy and benefit of currently available treatments. Emerging data have shown that other SSRs may regulate the sites at which ER binds to DNA in ways that can powerfully suppress the oncogenic activity of ER in breast cancer. This includes the progesterone receptor (PR) that was recently shown to reprogram the ER DNA binding landscape towards genes associated with a favourable outcome. Another attractive candidate is the androgen receptor (AR), which is expressed in the majority of breast cancers and inhibits growth of the normal breast and ER-positive tumours when activated by ligand. These findings have led to the initiation of breast cancer clinical trials evaluating therapies that selectively harness the ability of SSRs to ‘push’ ER towards anti-tumorigenic activity. Our review will focus on the established and emerging clinical evidence for activating PR or AR in ER-positive breast cancer to inhibit the tumour growth-promoting functions of ER.
Keywords: Estrogen receptor; endocrine therapy; endocrine resistance; breasst cancer; progesterone receptor; androgen receptor
Rights: © 2016 Society for Endocrinology Published by Bioscientifica Ltd. Printed in Great Britain
RMID: 0030056724
DOI: 10.1530/ERC-16-0427
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