title: A chemical probe toolbox for dissecting the cancer epigenome.
abstract: Cancer cell hallmarks are underpinned by transcriptional programmes operating in the context of a dynamic and complicit epigenomic environment. Somatic alterations of chromatin modifiers are among the most prevalent cancer perturbations. There is a pressing need for targeted chemical probes to dissect these complex, interconnected gene regulatory circuits. Validated chemical probes empower mechanistic research while providing the pharmacological proof of concept that is required to translate drug-like derivatives into therapy for cancer patients. In this Review, we describe chemical probe development for epigenomic effector proteins that are linked to cancer pathogenesis. By annotating these reagents, we aim to share our perspectives on an informative 'epigenomic toolbox' of broad utility to the research community.
authors.affiliation: Gene Regulation Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3052, Australia.|School of Clinical Sciences at Monash Health, Monash University, Clayton 3168, Australia.
authors.forename: Jake
authors.initials: J
authors.lastname: Shortt
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.|Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts 02142, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ott
authors.affiliation: Gene Regulation Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3052, Australia.
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.|Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts 02142, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
mesh_terms: D000818:Animals; D019175:DNA Methylation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000037:antagonists & inhibitors; D057890:Epigenomics; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D056466:Histone Demethylases / Q000037:antagonists & inhibitors; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D037761:Sirtuins / Q000037:antagonists & inhibitors
chemical_list: D056466:Histone Demethylases; D000076983:Histone Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D037761:Sirtuins