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Vorinostat

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Nature Reviews Drug Discovery volume 6, pages 21–22 (2007)Cite this article

Abstract

Vorinostat (Zolinza; Merck) was approved by the US FDA in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. It is the first in a new class of anticancer agents that inhibit histone deacetylases, which have a key role in the epigenetic regulation of gene expression.

References

  1. Yoo, C. B. & Jones, P. A. Epigenetic therapy of cancer: past, present and future. Nature Rev. Drug Discov. 5, 37–50 (2006).

    Article  CAS  Google Scholar 

  2. Bolden, J. E., Peart, M. J. & Johnstone, R. W. Anticancer activities of histone deacetylase inhibitors. Nature Rev. Drug Discov. 5, 769–784 (2006).

    Article  CAS  Google Scholar 

  3. Richon, V. M. et al. Second generation hybrid polar compounds are potent inducers of transformed cell differentiation. Proc. Natl Acad. Sci. USA 93, 5705–5708 (1996)

    Article  CAS  Google Scholar 

  4. Richon, V. M. et al. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc. Natl Acad. Sci. USA 95, 3003–3007 (1998).

    Article  CAS  Google Scholar 

  5. Yoshida, M. et al. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J. Biol. Chem. 265, 17174–17179 (1990).

    CAS  PubMed  Google Scholar 

  6. FDA labelling information [online], (2006).

  7. Kelly, W. K. & Marks, P. A. Drug insight: Histone deacetylase inhibitors — development of the new targeted anticancer agent suberoylanilide hydroxamic acid. Nature Clin. Pract. Oncol. 2, 150–157 (2005).

    Article  CAS  Google Scholar 

  8. Richon, V. M. et al. Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc. Natl Acad. Sci. USA 97, 10014–10019 (2000).

    Article  CAS  Google Scholar 

  9. Duvic, M. et al. Phase II trial of oral vorinostat (suberoylanilide hydroxamic Acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 7 Sep 2006 (doi: blood-2006-06-025999v1).

  10. Kim, E. J. et al. Immunopathogenesis and therapy of cutaneous T cell lymphoma. J. Clin. Invest. 115, 798–812 (2005).

    Article  CAS  Google Scholar 

  11. Bali, P. et al. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J. Biol. Chem. 280, 26729–26734 (2005).

    Article  CAS  Google Scholar 

  12. Trachootham, D. et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 10, 241–252 (2006).

    Article  CAS  Google Scholar 

  13. Ungerstedt, J. S. et al. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc. Natl Acad. Sci. USA 102, 673–678 (2005).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. the Division of Hematology/Oncology, Virginia Commonwealth University/Medical College of Virginia, Richmond, 23298, Virginia, USA

    Steven Grant

  2. IMS Health, 7 Harewood Avenue, London, NW1 6JB, UK

    Chris Easley

  3. Nature Reviews Drug Discovery,

    Peter Kirkpatrick

Authors

  1. Steven Grant
  2. Chris Easley
  3. Peter Kirkpatrick

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Grant, S., Easley, C. & Kirkpatrick, P. Vorinostat. Nat Rev Drug Discov 6, 21–22 (2007). https://doi.org/10.1038/nrd2227

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  • DOI: https://doi.org/10.1038/nrd2227

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