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Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer

Department of Medicine/Endocrinology, School of Medicine, University of Colorado, Ms 8106 PO Box 6511, 12801 E 17th Avenue, Aurora, Denver, CO 80010, USA; Tel.: +1-303-724-1013; Fax: +1-303-724-3920
Diseases 2017, 5(3), 16; https://doi.org/10.3390/diseases5030016
Received: 24 April 2017 / Revised: 28 June 2017 / Accepted: 30 June 2017 / Published: 6 July 2017
Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge. The precise mechanisms of endocrine resistance remain unclear. This is partly due to the complexity of the signaling pathways that influence the estrogen-mediated regulation in breast cancer. Mechanisms include ER modifications, alteration of coregulatory function and modification of growth factor signaling pathways. In this review, we provide an overview of epigenetic mechanisms of tamoxifen resistance in ER-positive luminal breast cancer. We highlight the effect of epigenetic changes on some of the key mechanisms involved in tamoxifen resistance, such as tumor-cell heterogeneity, ER signaling pathway and cancer stem cells (CSCs). It became increasingly recognized that CSCs are playing an important role in driving metastasis and tamoxifen resistance. Understanding the mechanism of tamoxifen resistance will provide insight into the design of novel strategies to overcome the resistance and make further improvements in breast cancer therapeutics. View Full-Text
Keywords: epigenetics; DNA methylation; histone modification; microRNA; luminal breast cancer; tamoxifen resistance; cancer stem cells epigenetics; DNA methylation; histone modification; microRNA; luminal breast cancer; tamoxifen resistance; cancer stem cells
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Abdel-Hafiz, H.A. Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer. Diseases 2017, 5, 16.

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