Mechanisms of resistance to histone deacetylase inhibitors Journal Article
| Authors: | Lee, J. H.; Choy, M. L.; Marks, P. A. |
| Article Title: | Mechanisms of resistance to histone deacetylase inhibitors |
| Abstract: | 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. © 2012 Elsevier Inc. |
| Keywords: | cancer chemotherapy; protein expression; histone deacetylase inhibitor; neutropenia; fluorouracil; liver cell carcinoma; solid tumor; gemcitabine; cancer radiotherapy; cell death; dna damage; dna repair; unindexed drug; bortezomib; multiple myeloma; gene expression; lung non small cell cancer; thrombocytopenia; weight reduction; in vivo study; cancer cell culture; in vitro study; cancer resistance; pruritus; drug fatality; hematologic malignancy; lung adenocarcinoma; protein synthesis; genomic instability; cancer cell; splenomegaly; tumor cell; ovary carcinoma; vorinostat; histone deacetylase inhibitors; reactive oxygen species; cell cycle arrest; chromosome breakage; autophagy; checkpoint kinase 1; nerve sheath tumor; histones; panobinostat; romidepsin; retinoic acid; azacitidine; valproic acid; pivaloyloxymethyl butyrate; belinostat; butyric acid; trichostatin a; acetylation; chloroquine; in vitro selection; n tert butyl 3 [5 methyl 2 [4 (4 methyl 1 piperazinyl)phenylamino] 4 pyrimidinylamino]benzenesulfonamide; stat protein; mocetinostat; dna double strand break; givinostat; entinostat; acquired resistance; autophagosome; endoplasmic reticulum stress; glucose regulated protein 78; bloom syndrome; oxamflatin; apicidin; resistance mechanisms; abexinostat; bafilomycin; dacinostat; quisinostat; tacedinaline; verlukast; thrombocyte disorder |
| Journal Title: | Advances in Cancer Research |
| Volume: | 116 |
| ISSN: | 0065-230X |
| Publisher: | Academic Press, Elsevier Inc |
| Date Published: | 2012-01-01 |
| Start Page: | 39 |
| End Page: | 86 |
| Language: | English |
| DOI: | 10.1016/b978-0-12-394387-3.00002-1 |
| PROVIDER: | scopus |
| PUBMED: | 23088868 |
| DOI/URL: | |
| Notes: | Chapter 2 in "Histone Deacetylase Inhibitors as Cancer Therapeutics" (ISBN: 978-0-12-394387-3) - "Export Date: 2 November 2012" - "CODEN: ACRSA" - "Source: Scopus" |
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