Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer

DNA methylation and histone modifications are important epigenetic modifications associated with gene (dys)regulation. The epigenetic modifications are balanced by epigenetic enzymes, so-called writers and erasers, such as DNA (de)methylases and histone (de)acetylases. Aberrant epigenetic alteration...

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Bibliographic Details
Published in:Breast cancer research : BCR 2014-07, Vol.16 (4), p.412-412, Article 412
Main Authors: Falahi, Fahimeh, van Kruchten, Michel, Martinet, Nadine, Hospers, Geke A P, Rots, Marianne G
Format: Article
Language:English
Subjects:
Analysis
Animals
Antimitotic agents
Antineoplastic agents
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cancer
Care and treatment
Clinical Trials as Topic
DNA (Cytosine-5-)-Methyltransferases - antagonists & inhibitors
DNA Methylation - drug effects
Drug Evaluation, Preclinical
Epigenesis, Genetic - drug effects
Epigenetic inheritance
Epigenomics
Female
Gene Expression Regulation, Neoplastic - drug effects
Genes
Genetic aspects
Health aspects
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylase Inhibitors - therapeutic use
Histones - metabolism
Humans
Methyltransferases
Review
Treatment Outcome
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Summary:DNA methylation and histone modifications are important epigenetic modifications associated with gene (dys)regulation. The epigenetic modifications are balanced by epigenetic enzymes, so-called writers and erasers, such as DNA (de)methylases and histone (de)acetylases. Aberrant epigenetic alterations have been associated with various diseases, including breast cancer. Since aberrant epigenetic modifications are potentially reversible, they might represent targets for breast cancer therapy. Indeed, several drugs have been designed to inhibit epigenetic enzymes (epi-drugs), thereby reversing epigenetic modifications. US Food and Drug Administration approval has been obtained for some epi-drugs for hematological malignancies. However, these drugs have had very modest anti-tumor efficacy in phase I and II clinical trials in breast cancer patients as monotherapy. Therefore, current clinical trials focus on the combination of epi-drugs with other therapies to enhance or restore the sensitivity to such therapies. This approach has yielded some promising results in early phase II trials. The disadvantage of epi-drugs, however, is genome-wide effects, which may cause unwanted upregulation of, for example, pro-metastatic genes. Development of gene-targeted epigenetic modifications (epigenetic editing) in breast cancer can provide a novel approach to prevent such unwanted events. In this context, identification of crucial epigenetic modifications regulating key genes in breast cancer is of critical importance. In this review, we first describe aberrant DNA methylation and histone modifications as two important classes of epigenetic mutations in breast cancer. Then we focus on the preclinical and clinical epigenetic-based therapies currently being explored for breast cancer. Finally, we describe epigenetic editing as a promising new approach for possible applications towards more targeted breast cancer treatment.
ISSN:1465-542X
1465-5411
1465-542X
DOI:10.1186/s13058-014-0412-z