Breast cancer treatments leads to variable responses. Hormonal therapy is beneficial to receptor positive breast cancer subtypes and display better clinical outcome than triple negative breast cancers (TNBCs) with FEC (5-Fluorouracil, Epirubicin and Cyclophosphamide) the mainstay chemotherapy regiment. Owning to their negative expressions of estrogen (ER), progesterone (PR) and HER2 receptors, disease recurrence and metastasis befalls some patients indicating resistance to FEC. Involvement of epigenetic silencing through DNA methylation, histone methylation, acetylation and sumoylation may be the key player in FEC chemoresistance. Epigenetic and molecular profiling successfully classified breast cancer subtypes, indicating potential driver mechanisms to the progression of TNBCs but functional mechanisms behind chemoresistance of these molecular markers are not well defined. Several epigenetic inhibitors and drugs have been used in the management of cancers but these attempts are mainly beneficial in hematopoietic cancers and not specifically favourable in solid tumours. Hypothetically, upon administration of epigenetic drugs, recovery of tumour suppressor genes is expected. However, high tendency of switching on global metastatic genes is predicted. Polycomb repressive complex (PRC) such as EZH2, SETD1A, DNMT, is known to have repressive effects in gene regulation and shown to inhibit cell proliferation and invasion in breast cancers. Individual epigenetic regulators may be an option to improve chemo-drug delivery in cancers. This review discussed on molecular signatures of various breast cancer subtypes and on-going attempts in understanding underlying molecular mechanisms of epigenetic regulators as well as providing insights on possible ways to utilize epigenetic enzymes/inhibitors with responses to chemotherapeutic drugs to re-program cellular and biological outcome in TNBCs.
CITATION STYLE
Hanif, E. A. M., & Shah, S. A. (2018, December 1). Overview on epigenetic re-programming: A potential therapeutic intervention in triple negative breast cancers. Asian Pacific Journal of Cancer Prevention. Asian Pacific Organization for Cancer Prevention. https://doi.org/10.31557/APJCP.2018.19.12.3341
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