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HDAC Inhibitors

An Emerging Anticancer Therapeutic Strategy

  • Chapter
Histone Deacetylases

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Coordinated and tight transcriptional regulation of genetic information is vital for maintenance of normal cell growth and differentiation. Cancer is typified by inappropriate gene expression-aberrant expression of genes associated with increased cellular proliferation and survival (e.g., oncogenes), as well as alterations in genes encoding tumor suppressor proteins. Therefore, targeting the gene expression machinery to restore its normalcy promises to be a useful anticancer therapeutic strategy. In the past, targeting the DNA binding multiprotein transcription factors with reasonable potency and specificity has been challenging owing to difficulties in disrupting protein-protein and protein-DNA interactions. However, recent studies showed that epigenetic modifications by enzymes play key roles in regulating gene expression, providing an opportunity to target such enzymes with small molecules for therapeutic purposes. Histone deacetylases (HDACs) can regulate gene expression by deacetylating histones, leading to repressed chromatin structure. In addition, HDACs can target nonhistone substrates, including several oncoproteins and tumor suppressors. Thus abnormal HDAC activity may lead to aberrant gene expression as well as perturbation in critical pathways. HDAC inhibitors have demonstrated efficacy in a variety of solid and hematological malignancies in early clinical trials. The current review focuses on the emerging utility of histone deacetylase inhibition as an anticancer therapeutic strategy.

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Authors and Affiliations

  1. Department of Oncology, Novartis Institutes for Biomedical Research, Cambridge, MA

    Paul Kwon, Meier Hsu & Peter Atadja PhD

  2. Department of Functional Genomics, Novartis Institutes for Biomedical Research, Cambridge, MA

    Dalia Cohen PhD

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  1. Paul Kwon
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  2. Meier Hsu
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  3. Dalia Cohen PhD
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  4. Peter Atadja PhD
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Editors and Affiliations

  1. Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA

    Eric Verdin MD

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© 2006 Humana Press Inc., Totowa, NJ

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Kwon, P., Hsu, M., Cohen, D., Atadja, P. (2006). HDAC Inhibitors. In: Verdin, E. (eds) Histone Deacetylases. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-024-3:315

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