Epigenetics of human cutaneous melanoma: Setting the stage for new therapeutic strategies

Luca Sigalotti, Alessia Covre, Elisabetta Fratta, Giulia Parisi, Francesca Colizzi, Aurora Rizzo, Riccardo Danielli, Hugues J M Nicolay, Sandra Coral, Michele Maio

Research output: Contribution to journalArticlepeer-review

Abstract

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects.

Original languageEnglish
Article number56
JournalJournal of Translational Medicine
Volume8
DOIs
Publication statusPublished - Jun 11 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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