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J Biomed Biotechnol. 2011;2011:514261. doi: 10.1155/2011/514261. Epub 2011 Jun 28.

Therapeutic strategies to enhance the anticancer efficacy of histone deacetylase inhibitors.

Author information

1
Department of Pediatrics Research, Children's Cancer Hospital, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

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.

PMID:
21765634
PMCID:
PMC3134392
DOI:
10.1155/2011/514261
[Indexed for MEDLINE]
Free PMC Article

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