2. Academic Validation
  3. Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy

Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy

  • Future Sci OA. 2019 Jan 29;5(3):FSO372. doi: 10.4155/fsoa-2018-0115.
Ali Alqahtani 1 1,  Khalil Choucair 2 2,  Mushtaq Ashraf 2 2,  Danae M Hammouda 2 2,  Abduraham Alloghbi 1 1,  Talal Khan 2 2,  Neil Senzer 2 2,  John Nemunaitis 2 3 2 3
Affiliations

Affiliations

  • 1 Department of Internal Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH, 43614, USA.
  • 2 Division of Hematology & Medical Oncology, Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH, 43614, USA.
  • 3 ProMedica Health System, Toledo, OH, 43606, USA.
PMID: 30906568 DOI: 10.4155/fsoa-2018-0115
Abstract

Histone lysine acetylation is critical in regulating transcription. Dysregulation of this process results in aberrant gene expression in various diseases, including Cancer. The bromodomain, present in several proteins, recognizes promotor lysine acetylation and recruits Other transcription factors. The bromodomain extra-terminal (BET) family of proteins consists of four conserved mammalian members that regulate transcription of oncogenes such as MYC and the NUT fusion oncoprotein. Targeting the acetyl-lysine-binding property of BET proteins is a potential therapeutic approach of Cancer. Consequently, following the demonstration that thienotriazolodiazepine small molecules effectively inhibit BET, clinical trials were initiated. We thus discuss the mechanisms of action of various BET inhibitors and the prospects for their clinical use as Cancer therapeutics.

Keywords

BET inhibitors; BET protein; cancer; clinical trials; combination therapy; hematological malignancies; solid tumors; targeted therapy.

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