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Targeting DNA methylation for epigenetic therapy.

Abstract
Patterns of DNA methylation are established during embryonic development and faithfully copied through somatic cell divisions. Based on current understanding of DNA methylation and other interrelated epigenetic modifications, a comprehensive view of the 'epigenetic landscape' and cancer epigenome is evolving. The cancer methylome is highly disrupted, making DNA methylation an excellent target for anticancer therapies. During the last few decades, an increasing number of drugs targeting DNA methylation have been developed to increase efficacy and stability and to decrease toxicity. The earliest and the most successful epigenetic drug to date, 5-Azacytidine, is currently recommended as the first-line treatment of high-risk myelodysplastic syndromes (MDS). Encouraging results from clinical trials have prompted further efforts to elucidate epigenetic alterations in cancer, and to subsequently develop new epigenetic therapies. This review delineates the latest cancer epigenetic models, the recent discovery of hypomethylation agents as well as their application in the clinic.
AuthorsXiaojing Yang, Fides Lay, Han Han, Peter A Jones
JournalTrends in pharmacological sciences (Trends Pharmacol Sci) Vol. 31 Issue 11 Pg. 536-46 (Nov 2010) ISSN: 1873-3735 [Electronic] England
PMID20846732 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • DNA Modification Methylases
  • Azacitidine
Topics
  • Antineoplastic Agents (therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Azacitidine (therapeutic use)
  • Clinical Trials as Topic
  • DNA Methylation
  • DNA Modification Methylases (antagonists & inhibitors, genetics, metabolism)
  • Epigenesis, Genetic (physiology)
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Myelodysplastic Syndromes (drug therapy, genetics)
  • Neoplasms (drug therapy, genetics)

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