Epigenetic Therapy in Breast Cancer

Division of Hematology and Oncology, Comprehensive Cancer Center, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA.
Current Breast Cancer Reports 03/2011; 3(1):34-43. DOI: 10.1007/s12609-010-0034-0
Source: PubMed


Breast carcinogenesis is a multistep process involving both genetic and epigenetic changes. Epigenetics is defined as reversible changes in gene expression, not accompanied by alteration in gene sequence. DNA methylation, histone modification, and nucleosome remodeling are the major epigenetic changes that are dysregulated in breast cancer. Several genes involved in proliferation, anti-apoptosis, invasion, and metastasis have been shown to undergo epigenetic changes in breast cancer. Because epigenetic changes are potentially reversible processes, much effort has been directed toward understanding this mechanism with the goal of finding effective therapies that target these changes. Both demethylating agents and the histone deacetylase inhibitors (HDACi) are under investigation as single agents or in combination with other systemic therapies in the treatment of breast cancer. In this review, we discuss the role of epigenetic regulation in breast cancer, in particular focusing on the clinical trials using therapies that modulate epigenetic mechanisms.

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    • "Despite growing advances in targeted therapies and screening techniques, breast cancer remains a leading cause of malignant mortality in women[1]. The onset and progression of breast cancer involve both genetic and epigenetic changes, and the latter are potentially reversible processes[2]. Histone deacetylase inhibitors (HDACIs), either alone or in combination with other agents, have consistently shown promise in clinical trials in the treatment of breast cancer[3]. "
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    ABSTRACT: Breast cancer is a leading malignancy among women with higher western countries, suggesting significant role for environmental factors in developing breast cancer. Recently, epigenetic modifications such as aberrant methylation and acetylation of genes and histones have been shown to play a critical role in breast cancer development. There are several articles published in the recent years with the major epigenetic signatures of breast cancer genes. Therefore compiling these information could lead to a greater understanding of the development of breast cancer and novel approaches for chemoprevention. Here we have provided different modes of epigenetic regulation including DNA methylation, histone modification, polycomb group of proteins, and non-coding RNAs. In addition, we have provided information on chemotherapeutic drugs that act through regulation of epigenetics and have progressed to clinical trials. Most importantly, we have analyzed the epigenetic regulation in the chemotherapy resistant breast cancer stem cell population. Furthermore, the epigenetic regulatory mechanisms of various breast cancer related genes are discussed in detail. Taken together, in this review we have discussed the current understanding of the modes of epigenetic regulation, and the epigenetic signatures seen in breast cancer. © 2013 Springer Science+Business Media Dordrecht. All rights are reserved.
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