Emerging roles of and therapeutic strategies targeting BRD4 in cancer

• Published in: Cellular immunology 2019-03, Vol.337, p.48-53
• Main Authors: White, Mary E., Fenger, Joelle M., Carson, William E.
• Format: Article
• Language: English
• Subjects: Animals; BET inhibitors; BRD4; Bromo- and Extra-Terminal (BET) protein family; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Transformation, Neoplastic - immunology; Chromatin Assembly and Disassembly - physiology; Epigenesis, Genetic - genetics; Gene Expression Regulation - genetics; Humans; Inflammation - metabolism; Inflammation and cancer; Neoplasms - pathology; Neoplasms - therapy; Nuclear Proteins - genetics; Proteins - antagonists & inhibitors; Proteins - metabolism; Proteins - physiology; Transcription Factors - antagonists & inhibitors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2019.02.001

•The BET protein family are important epigenetic regulators in cancer.•BET proteins are frequently deregulated in cancer.•Deregulation contributes to increased expression of oncogenes and pro-inflammatory cytokines.•These genes drive tumor inflammation, initiation, progression and metastasis. The Bromodomain and Extra-terminal (BET) family of proteins were first recognized as important epigenetic regulators in inflammatory processes; however, there is increasing evidence to support the notion that BET proteins also play a critical role in ‘reading’ chromatin and recruiting chromatin-regulating enzymes to control gene expression in a number of pathologic processes, including cancer. To this end, the mechanisms by which BET proteins regulate chromatin remodeling and promote tumor-associated inflammation have been heavily studied over the past decade. This article to review the biology of BET protein dysfunction in promoting tumor-associated inflammation and cancer progression and the application of small molecule inhibitors that target specific BET proteins, alone or in combination with immunomodulatory agents as a novel therapeutic strategy for cancer patients.