Mechanisms of Resistance to Histone Deacetylase Inhibitors

Histone deacetylase (HDAC) inhibitors are a new class of anticancer agents. HDAC inhibitors induce acetylation of histones and nonhistone proteins which are involved in regulation of gene expression and in various cellular pathways including cell growth arrest, differentiation, DNA damage and repair...

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Bibliographic Details
Published inAdvances in Cancer Research Vol. 116; pp. 39 - 86
Main Authors Lee, Ju-Hee, Choy, Megan L., Marks, Paul A.
Format Book Chapter Journal Article
LanguageEnglish
Published United States Elsevier Science & Technology 2012
Subjects
Acetylation
Acquired resistance
Animals
Autophagy
DNA double strand break
Drug Resistance, Neoplasm
Enzymology
Histone deacetylase inhibitors
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylases - chemistry
Histones
Humans
Microbiology (non-medical)
Neoplasm Proteins - antagonists & inhibitors
Neoplasms - drug therapy
Pharmacology
Reactive oxygen species
Resistance mechanisms
Signal Transduction - drug effects
Reactive oxygen species
Acquired resistance
Histone deacetylase inhibitors
DNA double strand break
Histones
Acetylation
Autophagy
Resistance mechanisms
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Summary:Histone deacetylase (HDAC) inhibitors are a new class of anticancer agents. HDAC inhibitors induce acetylation of histones and nonhistone proteins which are involved in regulation of gene expression and in various cellular pathways including cell growth arrest, differentiation, DNA damage and repair, redox signaling, and apoptosis (Marks, 2010). The U.S. Food and Drug Administration has approved two HDAC inhibitors, vorinostat and romidepsin, for the treatment of cutaneous T-cell lymphoma (Duvic & Vu, 2007; Grant et al., 2010; Marks & Breslow, 2007). Over 20 chemically different HDAC inhibitors are in clinical trials for hematological malignancies and solid tumors. This review considers the mechanisms of resistance to HDAC inhibitors that have been identified which account for the selective effects of these agents in inducing cancer but not normal cell death. These mechanisms, such as functioning Chk1, high levels of thioredoxin, or the prosurvival BCL-2, may also contribute to resistance of cancer cells to HDAC inhibitors.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ObjectType-Review-1
ISBN:0123943876
9780123943873
ISSN:0065-230X
2162-5557
DOI:10.1016/B978-0-12-394387-3.00002-1