Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies.
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.
Sigalotti
Luca
L
Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Via F, Gallini 2, Aviano, Italy. lsigalotti@cro.it
Covre
Alessia
A
Fratta
Elisabetta
E
Parisi
Giulia
G
Colizzi
Francesca
F
Rizzo
Aurora
A
Danielli
Riccardo
R
Nicolay
Hugues J M
HJ
Coral
Sandra
S
Maio
Michele
M
D019175:DNA Methylation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D035683:MicroRNAs / Q000378:metabolism; D011379:Prognosis; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012878:Skin Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*
D004791:Enzyme Inhibitors; D006657:Histones; D035683:MicroRNAs