QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.014167v1 68/4/917    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Acharya, M. R. Articles by Figg, W. D. Search for Related Content PubMed PubMed Citation Articles by Acharya, M. R. Articles by Figg, W. D.

MINIREVIEW

Rational Development of Histone Deacetylase Inhibitors as Anticancer Agents: A Review

Clinical Pharmacology Research Core, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (M.R.A., A.S., W.D.F.); and Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia (M.R.A., J.V.)

The epigenome is defined by DNA methylation patterns and the associated post-translational modifications of histones. This histone code determines the expression status of individual genes dependent upon their localization on the chromatin. The histone deacetylases (HDACs) play a major role in keeping the balance between the acetylated and deacetylated states of chromatin and eventually regulate gene expression. Recent developments in understanding the cancer cell cycle, specifically the interplay with chromatin control, are providing opportunities for developing mechanism-based therapeutic drugs. Inhibitors of HDACs are under considerable exploration, in part because of their potential roles in reversing the silenced genes in transformed tumor cells by modulating transcriptional processes. This review is an effort to summarize the nonclinical and clinical status of HDAC inhibitors currently under development in anticancer therapy.

Address correspondence to: Dr. William D. Figg, Clinical Pharmacology Research Core, National Cancer Institute, 9000 Rockville Pike, Building 10/Room 5A01, MSC1910, Bethesda, MD 20892. E-mail: wdfigg{at}helix.nih.gov

This article has been cited by other articles:

				S. E. Witta, R. Dziadziuszko, K. Yoshida, K. Hedman, M. Varella-Garcia, P. A. Bunn Jr, and F. R. Hirsch ErbB-3 expression is associated with E-cadherin and their coexpression restores response to gefitinib in non-small-cell lung cancer (NSCLC) Ann. Onc., April 1, 2009; 20(4): 689 - 695. [Abstract] [Full Text] [PDF]

				S. E. Wardell, O. R. Ilkayeva, H. L. Wieman, D. E. Frigo, J. C. Rathmell, C. B. Newgard, and D. P. McDonnell Glucose Metabolism as a Target of Histone Deacetylase Inhibitors Mol. Endocrinol., March 1, 2009; 23(3): 388 - 401. [Abstract] [Full Text] [PDF]

				P. Gallo, M. V.G. Latronico, P. Gallo, S. Grimaldi, F. Borgia, M. Todaro, P. Jones, P. Gallinari, R. De Francesco, G. Ciliberto, et al. Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure Cardiovasc Res, December 1, 2008; 80(3): 416 - 424. [Abstract] [Full Text] [PDF]

				C. Bonfils, A. Kalita, M. Dubay, L. L. Siu, M. A. Carducci, G. Reid, R. E. Martell, J. M. Besterman, and Z. Li Evaluation of the Pharmacodynamic Effects of MGCD0103 from Preclinical Models to Human Using a Novel HDAC Enzyme Assay Clin. Cancer Res., June 1, 2008; 14(11): 3441 - 3449. [Abstract] [Full Text] [PDF]

				A. Scuto, M. Kirschbaum, C. Kowolik, L. Kretzner, A. Juhasz, P. Atadja, V. Pullarkat, R. Bhatia, S. Forman, Y. Yen, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells Blood, May 15, 2008; 111(10): 5093 - 5100. [Abstract] [Full Text] [PDF]

				T. Suzuki and K. Nohara Regulatory Factors Involved in Species-specific Modulation of Arylhydrocarbon Receptor (AhR)-dependent Gene Expression in Humans and Mice J. Biochem., October 1, 2007; 142(4): 443 - 452. [Abstract] [Full Text] [PDF]

				Y.-Q. Cheng, M. Yang, and A. M. Matter Characterization of a Gene Cluster Responsible for the Biosynthesis of Anticancer Agent FK228 in Chromobacterium violaceum No. 968 Appl. Envir. Microbiol., June 1, 2007; 73(11): 3460 - 3469. [Abstract] [Full Text] [PDF]

				V. Baradari, A. Huether, M. Hopfner, D. Schuppan, and H. Scherubl Antiproliferative and proapoptotic effects of histone deacetylase inhibitors on gastrointestinal neuroendocrine tumor cells Endocr. Relat. Cancer, December 1, 2006; 13(4): 1237 - 1250. [Abstract] [Full Text] [PDF]

				Y. Kawai and I. J. Arinze Valproic Acid-Induced Gene Expression through Production of Reactive Oxygen Species. Cancer Res., July 1, 2006; 66(13): 6563 - 6569. [Abstract] [Full Text] [PDF]

				Z. A. Cao, K. E. Bass, S. Balasubramanian, L. Liu, B. Schultz, E. Verner, Y. Dai, R. A. Molina, J. R. Davis, S. Misialek, et al. CRA-026440: a potent, broad-spectrum, hydroxamic histone deacetylase inhibitor with antiproliferative and antiangiogenic activity in vitro and in vivo. Mol. Cancer Ther., July 1, 2006; 5(7): 1693 - 1701. [Abstract] [Full Text] [PDF]