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Epigenetics as a Therapeutic Target in Breast Cancer

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Epigenetics refers to alterations in gene expression due to modifications in histone acetylation and DNA methylation at the promoter regions of genes. Unlike genetic mutations, epigenetic alterations are not due to modifications in the gene primary nucleotide sequence. The importance of epigenetics in the initiation and progression of breast cancer has led many investigators to incorporate this novel and exciting field in breast cancer drug development. Several drugs that target epigenetic alterations, including inhibitors of histone deacetylase (HDAC) and DNA methyltransferase (DNMT), are currently approved for treatment of hematological malignancies and are available for clinical investigation in solid tumors. In this manuscript, we review the critical role of epigenetics in breast cancer including the potential for epigenetic alterations to serve as biomarkers determining breast cancer prognosis and response to therapy. We highlight initial promising results to date with use of epigenetic modifiers in patients with breast cancer and the ongoing challenges involved in the successful establishment of these agents for the treatment of breast cancer.

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Abbreviations

AZA:

5-azacitidine

CDA:

cytidine deaminase

CTCL:

cutaneous T-cell lymphoma

DAC:

decitabine

DNA:

deoxyribonucleic acid

DNMT:

DNA methyltransferase

DNMTs:

DNA methyltransferase enzymes

ER:

estrogen receptor

FDA:

Food and Drug Administration

HAT:

histone acetyltranserase

HDAC:

histone deacetylase

MDS:

myelodysplastic syndrome

miRNAs:

micro RNAs

mRNA:

messenger RNA

MSP:

methylation-specific polymerase chain reaction

uM:

micromolar

nM:

nanomolar

PARP:

poly(adenosine diphosphate)-ribose polymerase

PBMCs:

peripheral blood mononuclear cells

PTCL:

peripheral T-cell lymphoma

PR:

progesterone receptor

QM-MSP:

quantitative multiplex methylation-specific PCR

RNA:

ribonucleic acid

RT-PCR:

reverse transcriptase polymerase chain reaction

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

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Acknowledgements

Supported by Specialized Program Of Research Excellence in Breast Cancer (P50 CA88843), Stand Up To Cancer, and QVC and Fashion Footwear Association of New York (FFANY).

Disclosure

Dr. Stearns has received investigator-initiated grants from Abraxis, Merck, Novartis, and Pfizer.

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Connolly, R., Stearns, V. Epigenetics as a Therapeutic Target in Breast Cancer. J Mammary Gland Biol Neoplasia 17, 191–204 (2012). https://doi.org/10.1007/s10911-012-9263-3

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