EPIGENETIC TARGETING IN BREAST CANCER: THERAPEUTIC IMPACT AND FUTURE DIRECTION

Breast carcinogenesis is a multistep process involving both genetic and epigenetic changes. Epigenetics is defined as a reversible and heritable change in gene expression that is not accompanied by alteration in gene sequence. DNA methytation and histone modifications are the two major epigenetic changes that influence gene expression in cancer. The interaction between methylation and histone modification is intricately orchestrated by the formation of repressor complexes. Several genes involved in proliferation, antiapoptosis, invasion and metastasis have been shown to be methylated in various malignant and prematignant breast neoplasms. The histone deacetylase inhibitors (HDi) have emerged as an important class of drugs to be used synergistically with other systemic therapies in the treatment of breast cancer. Since epigenetic changes are potentially reversible processes, much effort has been directed toward understanding this mechanism with the goat of finding novel therapies as well as more refined diagnostic and prognostic tools in breast cancer.