Histone Deacetylase Inhibitors as a Treatment of Trail-Resistant Cancers

  • Jiri Neuzill
  • Ladislav Andera
  • Brian Gabrielli

Abstract

Histone deacetylas inhibitors (HDIs) are a novel prospective group of potential anti-cancer agents, some of them being tested in a clinical setting. The major mode of action of these compounds is inhibition of the cell cycle transition and, consequently, differential regulation of a number of genes necessary for cell proliferation, while favouring expression of genes rather associated with anti-proliferative pathways and with cell death signalling. This implies a possible role of HDIs in adjuvant treatment of tumours resistant to other agents, operating via a different molecular mechanism. The TNF-related apoptosis-inducing ligant (TRAIL) is a promising immunological inducer of apoptosis efficient against a variety of tumours with a remarkably selective mode of action. However, some malignancies are resistant to TRAIL treatment. In this paper, we review our current knowledge on HDI-mediated sensitisation of TRAIL-non-responsive tumours to this apoptogen and suggest a future clinical potential of HDIs and TRAIL in cancer management.

Key words

Apoptosis cell cycle arrest death receptor histone deacetylase inhibitor 

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Copyright information

© Springer 2005

Authors and Affiliations

  • Jiri Neuzill
    • 1
    • 2
  • Ladislav Andera
    • 2
  • Brian Gabrielli
    • 3
  1. 1.Apoptosis Research Group, School of Health ScienceGriffith UniversitySouthportAustralia
  2. 2.Laboratory of Cell Signalling and Apoptosis, Institute of Molecular GeneticsCzech Academy of SciencesPragueCzech Republic
  3. 3.University of QueenslandBrisbaneAustralia

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