title: Targeting epigenetic modifiers in cancer.
abstract: The chromatin structure of a gene plays an important role in regulating its expression. This structure is established through the action of various protein complexes that remodel nucleosomes, catalyse post-translational modifications, deposit histone variants and methylate DNA. Together these complexes establish epigenetic marks that influence expression of the gene. Some of these epigenetic marks are transient while others, such as those involved in silencing genes are more stable and can require several cell divisions to be fully implemented or reversed. Deregulated gene expression programs are a feature of cancer biology and it is now apparent that epigenetic changes, as well as genetic changes, are important in establishing these aberrant expression patterns. However, unlike genetic alterations, epigenetic changes are reversible. The complexes that catalyse these modifications therefore represent valuable targets for therapeutic intervention. Here we will review the most recent literature describing the protein complexes that catalyse epigenetic modifications and the inhibitors of these complexes that are being pursued as cancer drugs. In addition we will highlight those epigenetic modifiers that provide promise as therapeutic targets but for which inhibitors are not currently available.
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7001, Australia. A.F.Holloway@utas.edu.au
authors.forename: A F
authors.initials: AF
authors.lastname: Holloway
authors.forename: P C
authors.initials: PC
authors.lastname: Oakford
mesh_terms: D000818:Animals; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy
chemical_list: D006657:Histones; D015254:DNA Modification Methylases