Epigenetic regulation of breast cancer carcinogenesis

Abstract

Epigenetic mechanisms play a significant role in breast cancer (BC) pathogenesis and contribute to the tumor’s progression, metastasis and resistance to therapy. BC heterogeneity in large part is determined by unique epigenetic landscape created by various factors. However, despite obvious heterogeneity, modern therapeutic approaches in this disease are limited to evaluation of histological subtype, receptor status (estrogen, progesterone, human epidermal growth factor 2 receptors), and proliferative activity (Ki-67). All important oncogenes and tumor suppressor genes, as well as tumor microenvironment, are controlled by epigenetic factors, and study of these control mechanisms and identification of clinically significant epigenetic biomarkers is an important problem. Currently, there are thousands of studies on epigenetic regulation in BC, systematization of which will help to better understand complex mechanisms of carcinogenesis. This review describes the main epigenetic mechanisms including DNA and RNA methylation, histone post-translational modification, and regulatory activity of non-coding RNAs. Characteristics of epigenetic regulation of various molecular and biological BC subtypes taking into account diagnostic and prognostic markers are analyzed, potential therapeutic targets are evaluated. The article also considers signaling pathways regulated by epigenetic modulators.