Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Michael Dickinson, Ricky W. Johnstone, H. Miles Prince

ABSTRACT

The histone deacetylase inhibitors (HDACi) have demonstrated anticancer efficacy across a range of malignancies, most impressively in the hematological cancers. It is uncertain whether this clinical efficacy is attributable predominantly to their ability to induce apoptosis and differentiation in the cancer cell, or to their ability to prime the cell to other pro-death stimuli such as those from the immune system. HDACi-induced apoptosis occurs through altered expression of genes encoding proteins in both intrinsic and extrinsic apoptotic pathways; through effects on the proteasome/aggresome systems; through the production of reactive oxygen species, possibly by directly inducing DNA damage; and through alterations in the tumor microenvironment. In addition HDACi increase the immunogenicity of tumor cells and modulate cytokine signaling and potentially T-cell polarization in ways that may contribute the anti-cancer effect in vivo. Here, we provide an overview of current thinking on the mechanisms of HDACi activity, with attention given to the hematological malignancies as well as scientific observations arising from the clinical trials. We also focus on the immune effects of these agents. More... »

PAGES

3-20

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10637-010-9596-y

    DOI

    http://dx.doi.org/10.1007/s10637-010-9596-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1011776454

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21161327


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