Epigenetics of Breast Cancer: Clinical Status of Epi-drugs and Phytochemicals.

Epigenetics refers to alterations in gene expression due to differential histone modifications and DNA methylation at promoter sites of genes. Epigenetic alterations are reversible and are heritable during somatic cell division, but do not involve changes in nucleotide sequence. Epigenetic regulation plays a critical role in normal growth and embryonic development by controlling transcriptional activities of several genes. In last two decades, these modifications have been well recognized to be involved in tumor initiation and progression, which has motivated many investigators to incorporate this novel field in cancer drug development. Recently, growing number of epigenetic changes have been reported that are involved in the regulations of genes involved in breast tumor growth and metastasis. Drugs possessing epigenetic modulatory activities known as epi-drugs, mainly the inhibitors of histone deacetylases (HDACs) and DNA methyltransferases (DNMTs). Some of these drugs are undergoing different clinical trials for breast cancer treatment. Several phytochemicals such as green tea polyphenols, curcumin, genistein, resveratrol and sulforaphane have also been shown to alter epigenetic modifications in multiple cancer types including breast cancer. In this chapter, we summarize the role of epigenetic changes in breast cancer progression and metastasis. We have also discussed about various epigenetic modulators possessing chemopreventive and therapeutic efficacy against breast cancer with future perspectives.