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Epigenomics. 2010 Apr;2(2):221-32. doi: 10.2217/epi.10.1.

Epigenetic targets in human neoplasms.

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  • 1Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA.

Abstract

Epigenetic silencing of tumor suppressor genes is a salient feature of tumor cells. Re-expression of epigenetically silenced genes is a feasible and achievable strategy for cancer treatment. DNA methylation is the most characterized epigenetic silencing mechanism and the reversal of DNA methylation, genetically or pharmacologically, induces gene re-expression and proliferation arrest in tumor cells. Other epigenetic targets, such as histone acetylation and methylation, are also rational drug targets, and several small-molecule modulators of histone acetylation and methylation are currently under development or already in clinical trials. Epigenetic deregulation of miRNAs induces aberrant expression of miRNAs, which have been associated with the development and progression of cancer. The reversal of DNA methylation can induce the re-expression of miRNAs, and oligonucleotides can silence aberrantly expressed miRNAs. Evaluating the combination of different epigenetic modifiers and ensuring their optimization are the next challenges towards the establishment of epigenetic therapy.

PMID:
22121872
[PubMed - indexed for MEDLINE]
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