Journal
CANCER CELL
Volume 31, Issue 5, Pages 635-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2017.03.011
Keywords
-
Categories
Funding
- McKenna Claire Foundation
- Lyla Nsouli Foundation
- Alex's Lemonade Stand Foundation
- Cure Starts Now Foundation
- DIPG Collaborative
- Unravel Pediatric Cancer
- National Institute of Neurological Disorders and Stroke [R01NS092597]
- Department of Defense [NF140075]
- California Institute for Regenerative Medicine [CIRM RN3-06510]
- Childhood Brain Tumor Foundation
- V Foundation
- Joey Fabus Childhood Cancer Foundation
- Wayland Villars DIPG Foundation
- Connor Johnson, Zoey Ganesh, Abigail Jensen and Declan Gloster Memorial Funds
- N8 Foundation
- Godfrey Family Fund in Memory of Fiona Penelope, Virginia
- D.K. Ludwig Fund for Cancer Research
- Child Health Research Institute at Stanford Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer
- Liwei Wang Research Fund
- Recruitment Program of Global Experts of China (National 1000-Youth Talents Program)
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
- National Natural Science Foundation of China [81572761]
- Shanghai Rising-Star Program
- Howard Hughes Medical Institute [NIH R01 GM112720-01]
- March of Dimes Foundation
Ask authors/readers for more resources
Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. Identification of super-enhancers in DIPG provides insights toward the cell of origin, highlighting oligodendroglial lineage genes, and reveals unexpected mechanisms mediating tumor viability and invasion, including potassium channel function and EPH receptor signaling. The findings presented demonstrate transcriptional vulnerabilities and elucidate previously unknown mechanisms of DIPG pathobiology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available