Abstract
Breast cancer is a sporadic disease with genetic and epigenetic components. Genomic instability in breast cancer leads to mutations, copy number variations, and genetic rearrangements, while epigenetic remodeling involves alteration by DNA methylation, histone modification and microRNAs (miRNAs) of gene expression profiles. The accrued scientific findings strongly suggest epigenetic dysregulation in breast cancer pathogenesis though genomic instability is central to breast cancer hallmarks. Being reversible and plastic, epigenetic processes appear more amenable toward therapeutic intervention than the more unidirectional genetic alterations. In this review, we discuss the epigenetic reprogramming associated with breast cancer such as shuffling of DNA methylation, histone acetylation, histone methylation, and miRNAs expression profiles. As part of this, we illustrate how epigenetic instability orchestrates the attainment of cancer hallmarks which stimulate the neoplastic transformation-tumorigenesis-malignancy cascades. As reversibility of epigenetic controls is a promising feature to optimize for devising novel therapeutic approaches, we also focus on the strategies for restoring the epistate that favor improved disease outcome and therapeutic intervention.
Highlights
Breast cancer is a common cancer in women worldwide and was the highest (11.6%) newly diagnosed cancer type last year second only to lung cancer [1]
In order to illustrate the epigenetic profiles of breast cancer, we have considered epigenetic regulation in two different contexts (1) dynamic epigenetic regulation as exhibited by estrogen receptor (ER) expression in breast cancer and (2) noncannonical epigenetic regulation as shown by human telomerase reverse transcriptase expression during breast cancer
The epigenetic basis of breast cancer has come into light through many investigations over the last two decades
Summary
Breast cancer is a common cancer in women worldwide and was the highest (11.6%) newly diagnosed cancer type last year second only to lung cancer [1]. In the United States, the incidence rate of breast cancer shows a nearly steady trend, whereas the mortality started declining gradually from 1990 [3]. This decrease in mortality rate may be attributed to earlier cancer diagnosis and improved therapeutic intervention [2]. An epigenetic view of breast cancer is crucial to explain the molecular basis of breast cancer, improve therapeutic strategies, and to develop new therapeutic tools against breast cancer. All these factors contribute to moving beyond the genetic framework of breast cancer toward the epigenetic concept of breast cancer. We will cover epigenetic-based strategies against breast cancer such as the employment of epigenetic drugs, epigenetic diets, epigenome editing tools, and miRNA-based therapy
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