Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition

• Published in: Journal of neuropathology and experimental neurology Vol. 74; no. 8; pp. 778 - 790
• Main Authors: Taylor, Isabella C., Hütt-Cabezas, Marianne, Brandt, William D., Kambhampati, Madhuri, Nazarian, Javad, Chang, Howard T., Warren, Katherine E., Eberhart, Charles G., Raabe, Eric H.
• Format: Journal Article
• Language: English
• Published: England American Association of Neuropathologists, Inc 01.08.2015; by American Association of Neuropathologists, Inc
• Subjects: Animals; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Blotting, Western; Brain Stem Neoplasms - metabolism; Brain Stem Neoplasms - pathology; Fluorescent Antibody Technique; Glioma - metabolism; Glioma - pathology; Humans; Mice; Mice, Nude; N-Myc Proto-Oncogene Protein; Nuclear Proteins - metabolism; Oncogene Proteins - metabolism; Pons - metabolism; Pons - pathology; Radiation Tolerance - physiology; Xenograft Model Antitumor Assays; γ-secretase inhibitor; Pediatric brain tumor; Diffuse intrinsic pontine glioma; MRK003; HES; Radiation

NOTCH regulates stem cells during normal development and stemlike cells in cancer, but the roles of NOTCH in the lethal pediatric brain tumor diffuse intrinsic pontine glioma (DIPG) remain unknown. Because DIPGs express stem cell factors such as SOX2 and MYCN, we hypothesized that NOTCH activity wou...