Epigenetic Modifications as Therapeutic Targets

By T. Kelly, Daniel D. De Carvalho, Peter A. Jones. Nature Biotechnology, 2010

808 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7ac1db1b73f72508fe755fb4e0704d04579c8420

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Peter A. Jones
2. Mihai G. Netea

In Molecular Biology

1. Peter A. Jones
2. S. Baylin
3. G. Liang
4. Daniel D. De Carvalho
5. J. You
6. F. Lay
7. Xiaojing Yang
8. Han F Han

Citations in the corpus

• Gene Body Methylation can alter Gene Expression and is a Therapeutic Target in Cancer (2014, methodology): “Much effort has been invested to determine the molecular mechanisms underlining the clinical efficacies of 5-Aza-CR and 5-Aza-CdR (Heyn and Esteller, 2012; Kelly et al., 2010a).”
• Oxidized Low-Density Lipoprotein Induces Long-Term Proinflammatory Cytokine Production and Foam Cell Formation via Epigenetic Reprogramming of Monocytes (2014, background): “Particularly in the field of hematology and oncology, nonspecific methyltransferase inhibitors and histone deacetylase inhibitors are already used in clinical trials.(27) As a proof-of-concept Choi et al(28) showed that pharmacological modulation of histone acetylation can indeed modulate the develo”
• Epigenetic Determinants of Cancer. (2016, background): “The clinical successes with current epigenetic drugs have led to a big increase in interest from the pharmaceutical industry in developing compounds that will target epigenetic abnormalities in cancers (Kelly et al. 2010; Dawson et al. 2011; Arrowsmith et al. 2012).”
• Epigenetic protein families: a new frontier for drug discovery (2012, background): “DAC10-1(1) HAC10-5 HD10-2(1) H D AC (6)(1) H D A C 6(2) D A C 9 H D A C 5 HD AC 4 HD AC 7 HD AC 2 HD AC1 HDAC3 HAC8 HAC11 SIRT7 SIRT6 -2 SIR T6 -1 SI RT 64”
• Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications (2016, background): “One such inhibitor, 5Azacytidine, is well known to have good efficacy in treating myelodysplastic syndromes [72, 73].”
• Cancer Genetics and Epigenetics: Two Sides of the Same Coin? (2012, background): “Driver genes must be essential for cancer causation, whereas passenger genes are not necessary (Kelly et al., 2010).”