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PMID: 20944599 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Epigenetic modifications as therapeutic targets.

Nature biotechnology ·Vol. 28 ·No. 10 ·2010-10-00 ·Pages 1069-78

Kelly TK, De Carvalho DD, Jones PA

Abstract

Epigenetic modifications work in concert with genetic mechanisms to regulate transcriptional activity in normal tissues and are often dysregulated in disease. Although they are somatically heritable, modifications of DNA and histones are also reversible, making them good targets for therapeutic intervention. Epigenetic changes often precede disease pathology, making them valuable diagnostic indicators for disease risk or prognostic indicators for disease progression. Several inhibitors of histone deacetylation or DNA methylation are approved for hematological malignancies by the US Food and Drug Administration and have been in clinical use for several years. More recently, histone methylation and microRNA expression have gained attention as potential therapeutic targets. The presence of multiple epigenetic aberrations within malignant tissue and the abilities of cells to develop resistance suggest that epigenetic therapies are most beneficial when combined with other anticancer strategies, such as signal transduction inhibitors or cytotoxic treatments. A key challenge for future epigenetic therapies will be to develop inhibitors with specificity to particular regions of chromosomes, thereby potentially reducing side effects.

MeSH Terms
Antineoplastic Agents/therapeutic use DNA Methylation/drug effects Epigenesis, Genetic/drug effects Histone Deacetylase Inhibitors/therapeutic use Histones/metabolism Humans Neoplasms/drug therapy Nucleosides/therapeutic use
Chemicals
Antineoplastic Agents Histone Deacetylase Inhibitors Histones Nucleosides
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kelly Theresa K
Departments of Urology and Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
De Carvalho Daniel D
Jones Peter A
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Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
DOI
10.1038/nbt.1678
Published
2010-10-00
Pages
1069-78
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC3022972
Subset
IM
Grants
NCI NIH HHS · R35 CA049758-12 · United States
NCI NIH HHS · R37 CA082422 · United States
NCI NIH HHS · R01CA083867 · United States
NCI NIH HHS · R37CA082422 · United States
External Links
PubMed source DOI: 10.1038/nbt.1678 PMC Full Text View journal details
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