title: Targeting BET bromodomains for cancer treatment.
abstract: The bromodomain and extraterminal (BET) subfamily of bromodomain-containing proteins has emerged in the last few years as an exciting, novel target group. BRD4, the best studied BET protein, is implicated in a number of hematological and solid tumors. This is linked to its role in modulating transcription elongation of essential genes involved in cell cycle and apoptosis such as c-Myc and BCL2. Potent BET inhibitors with promising antitumor efficacy in a number of preclinical cancer models have been identified in recent years. This led to clinical studies focusing mostly on the treatment of leukemia and lymphoma, and first encouraging signs of efficacy have already been reported. Here we discuss the biology of BRD4, its known interaction partners and implication in different tumor types. Further, we summarize the current knowledge on BET bromodomain inhibitors.
authors.affiliation: Global Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany.|Institute of Chemistry & Biochemistry, Free University, D-14195 Berlin, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Jung
authors.affiliation: Global Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany.
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Gelato
authors.affiliation: Global Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany.
authors.forename: Amaury
authors.initials: A
authors.lastname: Fernández-Montalván
authors.affiliation: Global Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Siegel
authors.affiliation: Global Drug Discovery, Bayer Pharma AG, D-13353 Berlin, Germany.
authors.forename: Bernard
authors.initials: B
authors.lastname: Haendler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D000092468:Bromodomain Containing Proteins
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins
keywords: BET inhibitor; BRD4; bromodomain; c-Myc; chromatin; transcription control