Cutaneous melanoma is a lethal disease, even when diagnosed in advanced stages.,Although recent progress in biology and treatment has dramatically improved survival rates, new therapeutic approaches are still needed.,Deregulation of epigenetics, which mainly controls DNA methylation status and chromatin remodeling, is implied not only in cancer initiation and progression, but also in resistance to antitumor drugs.,Epigenetics in melanoma has been studied recently in both melanoma preclinical models and patient samples, highlighting its potential role in different phases of melanomagenesis, as well as in resistance to approved drugs such as immune checkpoint inhibitors and MAPK inhibitors.,This review summarizes what is currently known about epigenetics in melanoma and dwells on the recognized and potential new targets for testing epigenetic drugs, alone or together with other agents, in advanced melanoma patients.
Post-translational histone modifications such as acetylation and methylation can affect gene expression.,Histone acetylation is commonly associated with activation of gene expression whereas histone methylation is linked to either activation or repression of gene expression.,Depending on the site of histone modification, several histone marks can be present throughout the genome.,A combination of these histone marks can shape global chromatin architecture, and changes in patterns of marks can affect the transcriptomic landscape.,Alterations in several histone marks are associated with different types of cancers, and these alterations are distinct from marks found in original normal tissues.,Therefore, it is hypothesized that patterns of histone marks can change during the process of tumorigenesis.,This review focuses on histone methylation changes (both removal and addition of methyl groups) in malignant melanoma, a deadly skin cancer, and the implications of specific inhibitors of these modifications as a combinatorial therapeutic approach.