title: Targeting the histone orthography of cancer: drugs for writers, erasers and readers.
abstract: Gene expression is dynamically controlled by epigenetics through post-translational modifications of histones, chromatin-associated proteins and DNA itself. All these elements are required for the maintenance of chromatin structure and cell identity in the context of a normal cellular phenotype. Disruption of epigenetic regulation is a common event in human cancer. Here, we review the key protein families that control epigenetic signalling through writing, erasing or reading specific post-translational modifications. By exploiting the leading role of epigenetics in tumour development and the reversibility of epigenetic modifications, promising novel epigenetic-based therapies are being developed. In this article, we highlight the emerging low MW inhibitors targeting each class of chromatin-associated protein, their current use in preclinical and clinical trials and the likelihood of their being approved in the near future.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Simó-Riudalbas
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.|Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000187:drug effects*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D056466:Histone Demethylases / Q000037:antagonists & inhibitors*; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors*; D006657:Histones / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases