Abstract

Melanoma is a highly aggressive tumour with poor prognosis in the metastatic stage that arises and evolves due to a myriad of genetic and epigenetic events. Among these, the interaction between epigenetic alterations (i.e., DNA methylation, histone modifications, mRNA silencing by miRNAs and nucleosome repositioning) has been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, DNA repair, apoptosis, invasion and immune recognition. A number of new oncogene candidates such as MAPK1/2, ERBB4, GRIN2A, GRM3, RAC1, and PREX2 were identified. Their particular role in melanoma biology is currently under investigation. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (BRAF inhibitors and mitogen-activated protein kinase kinase [MEK] inhibitors) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. In this review, the risk factors, pathogenesis, and innovations in treatment of melanoma, synthetic small molecule inhibitors, combined therapies and current progress in the development of phytochemical therapies and new targets will be mentioned.

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