Overview on Epigenetic Re-programming: A Potential Therapeutic Intervention in Triple Negative Breast Cancers

Abstract

Breast cancer treatments leads to variable responses. Hormonal therapy is beneficial to receptor positive breast cancer<br />subtypes and display better clinical outcome than triple negative breast cancers (TNBCs) with FEC (5-Fluorouracil,<br />Epirubicin and Cyclophosphamide) the mainstay chemotherapy regiment. Owning to their negative expressions of<br />estrogen (ER), progesterone (PR) and HER2 receptors, disease recurrence and metastasis befalls some patients indicating<br />resistance to FEC. Involvement of epigenetic silencing through DNA methylation, histone methylation, acetylation and<br />sumoylation may be the key player in FEC chemoresistance. Epigenetic and molecular profiling successfully classified<br />breast cancer subtypes, indicating potential driver mechanisms to the progression of TNBCs but functional mechanisms<br />behind chemoresistance of these molecular markers are not well defined. Several epigenetic inhibitors and drugs have<br />been used in the management of cancers but these attempts are mainly beneficial in hematopoietic cancers and not<br />specifically favourable in solid tumours. Hypothetically, upon administration of epigenetic drugs, recovery of tumour<br />suppressor genes is expected. However, high tendency of switching on global metastatic genes is predicted. Polycomb<br />repressive complex (PRC) such as EZH2, SETD1A, DNMT, is known to have repressive effects in gene regulation and<br />shown to inhibit cell proliferation and invasion in breast cancers. Individual epigenetic regulators may be an option<br />to improve chemo-drug delivery in cancers. This review discussed on molecular signatures of various breast cancer<br />subtypes and on-going attempts in understanding underlying molecular mechanisms of epigenetic regulators as well<br />as providing insights on possible ways to utilize epigenetic enzymes/inhibitors with responses to chemotherapeutic<br />drugs to re-program cellular and biological outcome in TNBCs.