Archives of Toxicology

, Volume 88, Issue 9, pp 1651–1668 | Cite as

Epigenetic drugs against cancer: an evolving landscape

  • Antonella Di Costanzo
  • Nunzio Del Gaudio
  • Antimo Migliaccio
  • Lucia Altucci
Review Article


Alteration of the chromatin orchestra seems to play a critical role in cancer. In recent years, in-depth studies of epigenetic machinery and its deregulation have led to the development and use of a wide range of modulatory molecules directed not only at chromatin enzymes (histone acetyltransferases, histone deacetylases, histone methyltransferases, histone demethylases and DNA methyltransferases) but also toward the emerging class of chromatin-associated proteins, so-called “histone readers.” Chromatin modifiers are attractive therapeutic targets for the development of new cancer therapies. Many are currently approved by the US Food and Drug Administration and used to treat different malignancies. Specifically, inhibitors of DNA methyltransferases, such as azacitidine and decitabine, have been approved for the treatment of myelodysplastic syndrome, while inhibitors of histone deacetylases, including vorinostat and romidepsin, have been approved for cutaneous T-cell lymphoma. The bromodomain and extra-terminal inhibitors JQ1, IBET762 and IBET151 have performed extremely well in preclinical settings, suggesting that they may be promising molecules for the treatment of some type of tumors. This review focuses on epidrugs and their possible application, with particular emphasis on their mechanism of action as well as their present status in clinical and preclinical trials.


Epigenetics Chromatin modulation Cancer Drug discovery 



This work was supported by: EU, Blueprint project no. 282510; the Italian Flag Project: EPIGEN; AIRC No. 11812; PRIN-2012. We apologize to the authors whose work we could not cite due to reference restrictions. We wish to thank C. Fisher for linguistic editing of the manuscript.

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Antonella Di Costanzo
    • 1
  • Nunzio Del Gaudio
    • 1
  • Antimo Migliaccio
    • 1
  • Lucia Altucci
    • 1
  1. 1.Dipartimento di Biochimica, Biofisica e Patologia GeneraleSeconda Università degli Studi di NapoliNaplesItaly

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