ArticlePloS one2013
In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02758366 (An Open-label, Single-arm, Phase II Study to Evaluate Safety and Efficacy of Doxorubicin in Combination With Radiotherapy, Temozolomide and Valproic Acid in Patients With Glioblastoma Multiforme), which is not on this map. Cited by 84 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-label, Single-arm, Phase II Study to Evaluate Safety and Efficacy of Doxorubicin in Combination With Radiotherapy, Temozolomide and Valproic Acid in Patients With Glioblastoma Multiforme (GBM) and Diffuse Intrinsic Pontine Glioma (DIPG)
Who cites it
84 citing papers in PubMed, 136 citations in OpenAlex.
- Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas.Journal of neuro-oncology · 2015Trial
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- Consequences of irradiation on blood-brain tumor barrier model of Diffuse Midline Glioma: characterization of physical and metabolic properties.Fluids and barriers of the CNS · 2026Article
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- High-throughput in vitro drug screening and in vivo studies identify fenretinide as a brain-penetrant DMG therapeutic.Neuro-oncology · 2025Article
- Opportunities in the translational pipeline for pediatric brain cancer therapies.Pediatric research · 2025Review
- Opportunities and challenges for patient-derived models of brain tumors in functional precision medicine.NPJ precision oncology · 2025Review
- Pharmacological Phase I Clinical Trials in Pediatric Brain Tumors (1990-2024): A Historical Perspective.Oncology research · 2025Review
- Characteristics of the blood-brain barrier in pediatric brain tumors.Frontiers in pediatrics · 2025Review
- A Repurposed Drug Selection Pipeline to Identify CNS-Penetrant Drug Candidates for Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Oxime Linked Doxorubicin Glycoconjugates Improve the Specific Targeting of Glioblastoma in High-Grade Glioma Therapy.ACS medicinal chemistry letters · 2024Article
- The role of focused ultrasound for pediatric brain tumors: current insights and future implications on treatment strategies.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- The impact of ATP-binding cassette transporters in the diseased brain: Context matters.Cell reports. Medicine · 2024Review
- The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.Biology · 2024Review
- Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo.The Journal of pharmacology and experimental therapeutics · 2024Article
- A real-world analysis of FDA Adverse Event Reporting System (FAERS) events for liposomal and conventional doxorubicins.Scientific reports · 2024Article
- Targeting diffuse midline gliomas: The promise of focused ultrasound-mediated blood-brain barrier opening.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the leading cause of cancer-related death in children. While it is clear that surgery (if possible), and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear. Therefore, we performed an in vitro drug screen on primary glioma cells, including three DIPG cultures, to determine drug sensitivity of these tumours, without the possible confounding effect of insufficient drug delivery. This screen revealed a high in vitro cytotoxicity for melphalan, doxorubicine, mitoxantrone, and BCNU, and for the novel, targeted agents vandetanib and bortezomib in pHGG and DIPG cells. We subsequently determined the expression of the drug efflux transporters P-gp, BCRP1, and MRP1 in glioma cultures and their corresponding tumor tissues. Results indicate the presence of P-gp, MRP1 and BCRP1 in the tumor vasculature, and expression of MRP1 in the glioma cells themselves. Our results show that pediatric glioma and DIPG tumors per se are not resistant to chemotherapy. Treatment failure observed in clinical trials, may rather be contributed to the presence of drug efflux transporters that constitute a first line of drug resistance located at the blood-brain barrier or other resistance mechanism. As such, we suggest that alternative ways of drug delivery may offer new possibilities for the treatment of pediatric high-grade glioma patients, and DIPG in particular.
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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.