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Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies.
- Source :
-
Journal of translational medicine [J Transl Med] 2010 Jun 11; Vol. 8, pp. 56. Date of Electronic Publication: 2010 Jun 11. - Publication Year :
- 2010
-
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.
- Subjects :
- DNA Methylation drug effects
Enzyme Inhibitors pharmacology
Enzyme Inhibitors therapeutic use
Histones metabolism
Humans
Melanoma diagnosis
MicroRNAs metabolism
Prognosis
Protein Processing, Post-Translational drug effects
Skin Neoplasms diagnosis
Epigenesis, Genetic drug effects
Melanoma drug therapy
Melanoma genetics
Skin Neoplasms drug therapy
Skin Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 20540720
- Full Text :
- https://doi.org/10.1186/1479-5876-8-56