Document Detail


The clinical development of histone deacetylase inhibitors as targeted anticancer drugs.
MedLine Citation:
PMID:  20687783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IMPORTANCE OF THE FIELD: Histone deacetylase (HDAC) inhibitors are being developed as a new, targeted class of anticancer drugs.
AREA COVERED IN THIS REVIEW: This review focuses on the mechanisms of action of the HDAC inhibitors, which selectively induce cancer cell death.
WHAT THE READER WILL GAIN: There are 11 zinc-dependent HDACs in humans and the biological roles of these lysine deacetylases are not completely understood. It is clear that these different HDACs are not redundant in their activity. This review focuses on the mechanisms by which HDAC inhibitors can induce transformed cell growth arrest and cell death, inhibit cell mobility and have antiangiogenesis activity. There are more than a dozen HDAC inhibitors, including hydroxamates, cyclic peptides, benzamides and fatty acids, in various stages of clinical trials and many more compounds in preclinical development. The chemically different HDAC inhibitors may target different HDACs.
TAKE HOME MESSAGE: There are extensive preclinical studies with transformed cells in culture and tumor-bearing animal models, as well as limited clinical studies reported to date, which indicate that HDAC inhibitors will be most useful when used in combination with cytotoxic or other targeted anticancer agents.
Authors:
Paul A Marks
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  19     ISSN:  1744-7658     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2011-01-31     Revised Date:  2011-08-25    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1049-66     Citation Subset:  IM    
Affiliation:
Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Cell Biology and Genetics Program, 1275 York Ave, New York, NY 10065, USA. marksp@mskcc.org
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / pharmacology,  therapeutic use
Animals
Antineoplastic Agents / pharmacology*,  therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cell Death / drug effects
Cell Line, Tumor
Clinical Trials as Topic
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic / drug effects
Histone Deacetylase Inhibitors / pharmacology*,  therapeutic use*
Histone Deacetylases / metabolism
Humans
Mice
Molecular Targeted Therapy
Neoplasms / drug therapy*,  enzymology,  genetics
Zinc / metabolism
Grant Support
ID/Acronym/Agency:
P30CA08748-44/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antineoplastic Agents; 0/Histone Deacetylase Inhibitors; 7440-66-6/Zinc; EC 3.5.1.98/Histone Deacetylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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