Histone deacetylase inhibitors Journal Article


Authors: Marks, P. A.; Richon, V. M.; Miller, T.; Kelly, W. K.
Article Title: Histone deacetylase inhibitors
Abstract: The base sequence of DNA provides the genetic code for proteins. The regulation of expression or suppression of gene transcription is largely determined by the structure of the chromatin - referred to as epigenetic gene regulation (Agalioti et al., 2002; Jenuwein and Allis, 2001; Richards and Elgin, 2002; Spotswood and Turner, 2002; Zhang and Reinberg, 2001). Posttranslational modifications of the histones of chromatin play an important role in regulating gene expression. Some of the most extensively studied epigenetic modifications involve acetylationdeacetylation of lysines in the tails of the core histones, which is controlled by the action of histone deacetylases (HDACs) and histone acetyltransferases (HATs). A controlled balance between histone acetylation and deacetylation appears to be essential for normal cell growth (Waterborg, 2002). Alterations in the structure or expression of HATs and HDACs occur in many cancers (Jones and Baylin, 2002; Marks et al., 2001, 2003; Timmermann et al., 2001; Wang et al., 2001). A structurally diverse group of molecules has been developed that can inhibit HDACs (HDACi) (Arts et al., 2003; Bouchain and Delorme, 2003; Curtin and Glaser, 2003; Johnstone and Licht, 2003; Marks et al., 2003; Remiszewski, 2003; Richon et al., 1998; Yoshida et al., 2003). These inhibitors induce growth arrest, differentiation, andor apoptosis of cancer cells in vitro and in in vivo tumor-bearing animal models. Clinical trials with several of these agents have shown that certain HDACi have antitumor activity against various cancers at doses that are well tolerated by patients (Gottlicher et al., 2001; Kelly et al., 2002a,b; Piekarz et al., 2001; Wozniak et al., 1999).
Keywords: unclassified drug; histone deacetylase inhibitor; clinical trial; constipation; drug activity; drug tolerability; fatigue; neutropenia; paresthesia; review; diarrhea; nonhuman; solid tumor; antineoplastic agents; capecitabine; paclitaxel; anorexia; animals; mice; cell cycle; carboplatin; apoptosis; enzyme inhibition; infection; pharmacodynamics; gene expression; anemia; cell growth; lung non small cell cancer; nausea; thrombocytopenia; vomiting; dehydration; neoplasm proteins; bone pain; genetic transcription; cell differentiation; antineoplastic activity; enzyme activity; drug evaluation, preclinical; fever; drug synergism; gene expression regulation; confusion; hypoalbuminemia; hypokalemia; hyponatremia; malaise; depression; gene expression regulation, neoplastic; peripheral t cell lymphoma; hematologic malignancy; transcription regulation; protein processing, post-translational; drug mechanism; enzyme inhibitors; epigenetics; histone; glioblastoma; cancer cell; lymphoma; promyelocytic leukemia; vorinostat; muscle weakness; anxiety disorder; malignant neoplastic disease; dna sequence; models, molecular; headache; heart arrhythmia; somnolence; dyspepsia; hand foot syndrome; lethargy; genetic code; histone deacetylases; retinoic acid; clinical trials; lysine; azacitidine; acetyltransferases; granulocytopenia; valproic acid; histone deacetylase; deacetylation; protein modification; 3 phenylsulfamoylcinnamohydroxamic acid; arylbutyric acid derivative; n (2 aminophenyl) 4 (3 pyridinylmethoxycarbonylaminomethyl)benzamide; 4 [n (2 hydroxyethyl) n [2 (3 indolyl)ethyl]aminomethyl]cinnamohydroxamic acid; 4 n acetyldinaline; trichostatin a; acetylation; hypocalcemia; ecg abnormality; chromatin structure; skin lymphoma; disorientation; bone marrow tumor; hyperammonemia; appetite disorder; phenylacetic acid; histone acetyltransferase; histone acetyltransferases; fr 901228; oxamflatin; 6 (1,3 dioxo 1h,3h benzo[de]isoquinolin 2 yl) n hydroxyhexanamide; pyroxamide; apicidin; cancer; humans; human; male; female; priority journal; 3 carboxycinnamic acid bishydroxamide; slurred speech
Journal Title: Advances in Cancer Research
Volume: 91
ISSN: 0065-230X
Publisher: Academic Press, Elsevier Inc  
Date Published: 2004-01-01
Start Page: 137
End Page: 168
Language: English
DOI: 10.1016/s0065-230x(04)91004-4
PROVIDER: scopus
PUBMED: 15327890
DOI/URL:
Notes: Chapter in "Advances in Cancer Research" (ISBN: 978-0-12-006691-9) -- Cited By (since 1996):318 -- Export Date: 16 June 2014 -- CODEN: ACRSA -- Source: Scopus
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MSK Authors
  1. William K Kelly
    112 Kelly
  2. Paul Marks
    143 Marks
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