ArticleJournal of neuropathology and experimental neurology2015
Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition.
Article in Journal of neuropathology and experimental neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 75 citations in OpenAlex.
- Boosting CAR T cell functionality with oncolytic viruses for the treatment of pediatric diffuse midline gliomas.Molecular therapy. Oncology · 2026Article
- A live cell biosensor protocol for high-resolution screening of therapy-resistant cancer cells.PloS one · 2026Article
- A live cell biosensor protocol for high-resolution screening of therapy-resistant cancer cells.bioRxiv : the preprint server for biology · 2025Article
- Opportunities and challenges for patient-derived models of brain tumors in functional precision medicine.NPJ precision oncology · 2025Review
- The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles.Molecular therapy. Oncology · 2024Article
- The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.Biology · 2024Review
- Diffuse intrinsic pontine glioma (DIPG): A review of current and emerging treatment strategies.Cancer letters · 2024Review
- Targeting pediatric cancers via T-cell recognition of the monomorphic MHC class I-related protein MR1.Journal for immunotherapy of cancer · 2024Article
- Novel insights on genetics and epigenetics as clinical targets for paediatric astrocytoma.Clinical and translational medicine · 2024Review
- PRMT5 inhibition shows in vitro efficacy against H3K27M-altered diffuse midline glioma, but does not extend survival in vivo.Scientific reports · 2024Article
- Therapeutically targeting the unique disease landscape of pediatric high-grade gliomas.Frontiers in oncology · 2024Review
- Radiotherapy and radio-sensitization in H3CNS neuroscience & therapeutics · 2023Review
- Advances on Epigenetic Drugs for Pediatric Brain Tumors.Current neuropharmacology · 2023Review
- Article
- The Intricate Epigenetic and Transcriptional Alterations in Pediatric High-Grade Gliomas: Targeting the Crosstalk as the Oncogenic Achilles' Heel.Biomedicines · 2022Review
- Bromodomain and Extra-Terminal Protein Inhibitors: Biologic Insights and Therapeutic Potential in Pediatric Brain Tumors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG.Epigenetics & chromatin · 2022Article
- Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.Cancers · 2022Review
- Pharmaco-proteogenomic profiling of pediatric diffuse midline glioma to inform future treatment strategies.Oncogene · 2022Review
- Epigenetic programming of pediatric high-grade glioma: Pushing beyond proof of concept to clinical benefit.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
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 would be critical for DIPG growth. We determined that primary DIPGs expressed high levels of NOTCH receptors, ligands, and downstream effectors. Treatment of the DIPG cell lines JHH-DIPG1 and SF7761 with the γ-secretase inhibitor MRK003 suppressed the level of the NOTCH effectors HES1, HES4, and HES5; inhibited DIPG growth by 75%; and caused a 3-fold induction of apoptosis. Short hairpin RNAs targeting the canonical NOTCH pathway caused similar effects. Pretreatment of DIPG cells with MRK003 suppressed clonogenic growth by more than 90% and enhanced the efficacy of radiation therapy. The high level of MYCN in DIPG led us to test sequential therapy with the bromodomain inhibitor JQ1 and MRK003, and we found that JQ1 and MRK003 inhibited DIPG growth and induced apoptosis. Together, these results suggest that dual targeting of NOTCH and MYCN in DIPG may be an effective therapeutic strategy in DIPG and that adding a γ-secretase inhibitor during radiation therapy may be efficacious initially or during reirradiation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.