ArticlePloS one2015
A high-throughput in vitro drug screen in a genetically engineered mouse model of diffuse intrinsic pontine glioma identifies BMS-754807 as a promising therapeutic agent.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
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- Mendelian Randomization and Single-Cell RNA Sequencing Reveal CKAP4 and PFDN5 as Tumor Cell-Specific Causal Genes for Glioblastoma.International journal of general medicine · 2026Article
- Current State-of-the-Art Animal Models of Pediatric Brain Tumors.Brain sciences · 2025Review
- High-throughput in vitro drug screening and in vivo studies identify fenretinide as a brain-penetrant DMG therapeutic.Neuro-oncology · 2025Article
- Targeting the CD40 costimulatory receptor to improve virotherapy efficacy in diffuse midline gliomas.Cell reports. Medicine · 2025Article
- Recapitulating the immune microenvironment in pediatric brain cancer: preclinical modeling strategies.Frontiers in immunology · 2025Review
- The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.Neuro-oncology · 2024Article
- PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma.The Journal of clinical investigation · 2024Article
- Preclinical pediatric brain tumor models for immunotherapy: Hurdles and a way forward.Neuro-oncology · 2024Review
- Feasibility of probe washing after stereotactic needle biopsy as a novel technique for developing cell lines and xenografts of H3 K27-altered diffuse midline gliomas.Journal of neurosurgery. Pediatrics · 2023Article
- Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors.JAMA network open · 2023Article
- A novel CDK4/6 inhibitor combined with irradiation demonstrates potent anti-tumor efficacy in diffuse midline glioma.Journal of neuro-oncology · 2023Article
- Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.Cancers · 2023Review
- Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas.Neuro-oncology · 2023Article
- Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant.Neuro-oncology · 2022Article
- Exploiting 4-1BB immune checkpoint to enhance the efficacy of oncolytic virotherapy for diffuse intrinsic pontine gliomas.JCI insight · 2022Article
- Repurposing Vandetanib plus Everolimus for the Treatment ofCancer discovery · 2022Article
- Receptor tyrosine kinase (RTK) targeting in pediatric high-grade glioma and diffuse midline glioma: Pre-clinical models and precision medicine.Frontiers in oncology · 2022Review
- The current landscape of immunotherapy for pediatric brain tumors.Nature cancer · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Diffuse intrinsic pontine gliomas (DIPGs) represent a particularly lethal type of pediatric brain cancer with no effective therapeutic options. Our laboratory has previously reported the development of genetically engineered DIPG mouse models using the RCAS/tv-a system, including a model driven by PDGF-B, H3.3K27M, and p53 loss. These models can serve as a platform in which to test novel therapeutics prior to the initiation of human clinical trials. In this study, an in vitro high-throughput drug screen as part of the DIPG preclinical consortium using cell-lines derived from our DIPG models identified BMS-754807 as a drug of interest in DIPG. BMS-754807 is a potent and reversible small molecule multi-kinase inhibitor with many targets including IGF-1R, IR, MET, TRKA, TRKB, AURKA, AURKB. In vitro evaluation showed significant cytotoxic effects with an IC50 of 0.13 μM, significant inhibition of proliferation at a concentration of 1.5 μM, as well as inhibition of AKT activation. Interestingly, IGF-1R signaling was absent in serum-free cultures from the PDGF-B; H3.3K27M; p53 deficient model suggesting that the antitumor activity of BMS-754807 in this model is independent of IGF-1R. In vivo, systemic administration of BMS-754807 to DIPG-bearing mice did not prolong survival. Pharmacokinetic analysis demonstrated that tumor tissue drug concentrations of BMS-754807 were well below the identified IC50, suggesting that inadequate drug delivery may limit in vivo efficacy. In summary, an unbiased in vitro drug screen identified BMS-754807 as a potential therapeutic agent in DIPG, but BMS-754807 treatment in vivo by systemic delivery did not significantly prolong survival of DIPG-bearing mice.
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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.