As chromatin readers, the BET proteins (such as BRD3 and BRD4) bind to acetylated lysine residues on histone proteins and play important roles in the transcription of oncogenes such as MYC and MYCN. BET inhibitors, such as JQ1 and OTX-015, competitively bind to acetyl–lysine recognition pockets, displace BET bromodomain proteins from chromatin, and inhibit the expression of oncogenes, leading to cancer cell growth inhibition and apoptosis. BET inhibitors have shown promising in vitro and in vivo anticancer effects against MB, NUT-midline carcinoma, multiple myeloma, lymphoma, leukemia, and neuroblastoma. How- ever, treatment with BET protein inhibitors alone does not cause cancer remission in MB-bearing mice.
Author(s) Details:
Matthew J. Kling,
Department of Oral Biology, Creighton University, School of Dentistry, Omaha, NE 68102, USA and Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Varun Kesherwani,
Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Nitish K. Mishra,
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Gracey Alexander,
Department of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Erin M. McIntyre,
Department of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Sutapa Ray,
Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA and Department of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Kishore B. Challagundla,
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Shantaram S. Joshi,
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Don W. Coulter,
Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA and Department of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Nagendra K. Chaturvedi,
Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA and Department of Pediatrics, Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE 68198, USA and Department of Pediatrics, Hematology and Oncology Division, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE 68198, USA.