title: EZH2: an emerging role in melanoma biology and strategies for targeted therapy.
abstract: Histone modifications are increasingly being recognized as important epigenetic mechanisms that govern chromatin structure and gene expression. EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), responsible for tri-methylation of lysine 27 on histone 3 (H3K27me3) that leads to gene silencing. This highly conserved histone methyltransferase is found to be overexpressed in many different types of cancers including melanoma, where it is postulated to abnormally repress tumor suppressor genes. Somatic mutations have been identified in approximately 3% of melanomas, and activating mutations described within the catalytic SET domain of EZH2 confer its oncogenic activity. In the following review, we discuss the evidence that EZH2 is an important driver of melanoma progression and we summarize the progress of EZH2 inhibitors against this promising therapeutic target.
authors.affiliation: Melanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW, Australia.
authors.forename: Jessamy
authors.initials: J
authors.lastname: Tiffen
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Gallagher
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
mesh_terms: D000818:Animals; D018450:Disease Progression; D044127:Epigenesis, Genetic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D063151:Polycomb Repressive Complex 2
keywords: EZH2; H3K27me3; epigenetics; histone methyltransferase; melanoma; small molecule inhibitor