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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 514261, 17 pages
http://dx.doi.org/10.1155/2011/514261
Review Article

Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

1Department of Pediatrics Research, Children's Cancer Hospital, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
2The Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
3Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
4Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA

Received 11 August 2010; Accepted 11 March 2011

Academic Editor: Patrick Matthias

Copyright © 2011 Claudia P. Miller et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi) has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.