This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Camphausen, K. Articles by Tofilon, P. J. Search for Related Content PubMed PubMed Citation Articles by Camphausen, K. Articles by Tofilon, P. J. Social Bookmarking                            What's this?

Inhibition of Histone Deacetylation: A Strategy for Tumor Radiosensitization

Kevin Camphausen, Philip J. Tofilon

From the Radiation Oncology Branch, National Cancer Institute, Bethesda, MD; and the Department of Interdisciplinary Oncology, Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL

Address reprint requests to Kevin Camphausen, MD, Radiation Oncology Branch, National Cancer Institute, 10 Center Dr, Building 10 CRC B2-3562, Bethesda, MD 20892; e-mail: camphauk{at}mail.nih.gov

Recently, strategies to enhance tumor radiosensitivity have begun to focus on targeting the molecules and processes that regulate cellular radioresponse. A molecular target that has begun to receive considerable attention is histone acetylation. Histone acetylation is determined by the dynamic interaction of two families of enzymes: histone acetylases and histone deacetylases (HDACs). Histone acetylation plays a role in regulating chromatin structure and gene expression—two parameters that have long been considered determinants of radioresponse. As a means of modifying histone acetylation status, considerable effort has been put into the development of inhibitors of HDAC activity. This has led to the generation of a relatively large number of structurally diverse compounds that can inhibit HDAC activity resulting in histone hyperacetylation. Many of the newer HDAC inhibitor compounds have been designed with better bioavailability or pharmacology than the first-generation compounds. Whereas a number of these second-generation HDAC inhibitors have antitumor activity in preclinical cancer models when delivered as single agents, early clinical data demonstrate only cytostasis when used as monotherapy. However, recent preclinical studies have indicated that HDAC inhibitors from structurally diverse classes can enhance both the in vitro and in vivo radiosensitivity of human tumor cell lines generated from a spectrum of solid tumors. HDAC inhibitors are in clinical trials as single modalities, in combination with chemotherapeutic agents, and recently, in combination with radiotherapy.

Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. S. Schrump Cytotoxicity Mediated by Histone Deacetylase Inhibitors in Cancer Cells: Mechanisms and Potential Clinical Implications Clin. Cancer Res., June 15, 2009; 15(12): 3947 - 3957. [Abstract] [Full Text] [PDF]

				A. Baschnagel, A. Russo, W. E. Burgan, D. Carter, K. Beam, D. Palmieri, P. S. Steeg, P. Tofilon, and K. Camphausen Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts Mol. Cancer Ther., June 1, 2009; 8(6): 1589 - 1595. [Abstract] [Full Text] [PDF]

				T. Toyooka and Y. Ibuki Histone Deacetylase Inhibitor Sodium Butyrate Enhances the Cell Killing Effect of Psoralen plus UVA by Attenuating Nucleotide Excision Repair Cancer Res., April 15, 2009; 69(8): 3492 - 3500. [Abstract] [Full Text] [PDF]

				P. Chinnaiyan, D. Cerna, W. E. Burgan, K. Beam, E. S. Williams, K. Camphausen, and P. J. Tofilon Postradiation Sensitization of the Histone Deacetylase Inhibitor Valproic Acid Clin. Cancer Res., September 1, 2008; 14(17): 5410 - 5415. [Abstract] [Full Text] [PDF]