ArticleNeurosurgery2020
ABC Transporter Inhibition Plus Dexamethasone Enhances the Efficacy of Convection Enhanced Delivery in H3.3K27M Mutant Diffuse Intrinsic Pontine Glioma.
Article in Neurosurgery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Scientometric analysis of glioblastoma and blood-brain barrier research (1995-2024): evolving trends and therapeutic challenges.Frontiers in oncology · 2025Pooled it
- Article
- Enhanced plasma and brain concentrations and medulloblastoma cytotoxicity of asciminib and nilotinib by P-glycoprotein inhibition with tariquidar.Anti-cancer drugs · 2025Article
- Advances in the Repurposing and Blood-Brain Barrier Penetrance of Drugs in Pediatric Brain Tumors.Cancers · 2025Review
- Exosomes as drug delivery systems in glioma immunotherapy.Journal of nanobiotechnology · 2024Review
- Emerging Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma: A Systematic Review.Healthcare (Basel, Switzerland) · 2023Review
- Real-time sensing of MAPK signaling in medulloblastoma cells reveals cellular evasion mechanism counteracting dasatinib blockade of ERK activation during invasion.Neoplasia (New York, N.Y.) · 2020Article
- Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma.Current oncology reports · 2020Review
- Evaluating infusate parameters for direct drug delivery to the brainstem: a comparative study of convection-enhanced delivery versus osmotic pump delivery.Neurosurgical focus · 2020Article
- ABC Transporters at the Blood-Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas.Pharmaceutics · 2019Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAn impermeable blood-brain barrier and drug efflux via ATP-binding cassette (ABC) transporters such as p-glycoprotein may contribute to underwhelming efficacy of peripherally delivered agents to treat diffuse intrinsic pontine glioma (DIPG).
objectiveTo explore the pharmacological augmentation of convection-enhanced delivery (CED) infusate for DIPG.
methodsThe efficacy of CED dasatinib, a tyrosine kinase inhibitor, in a transgenic H3.3K27M mutant murine model was assessed. mRNA expression of ABCB1 (p-glycoprotein) was analyzed in 14 tumor types in 274 children. In Vitro viability studies of dasatinib, the p-glycoprotein inhibitor, tariquidar, and dexamethasone were performed in 2 H3.3K27M mutant cell lines. Magnetic resonance imaging (MRI) was used to evaluate CED infusate (gadolinium/dasatinib) distribution in animals pretreated with tariquidar and dexamethasone. Histological assessment of apoptosis was performed.
resultsContinuous delivery CED dasatinib improved median overall survival (OS) of animals harboring DIPG in comparison to vehicle (39.5 and 28.5 d, respectively; P = .0139). Mean ABCB1 expression was highest in K27M gliomas. In Vitro, the addition of tariquidar and dexamethasone further enhanced the efficacy of dasatinib (P < .001). In Vivo, MRI demonstrated no difference in infusion dispersion between animals pretreated with dexamethasone plus tariquidar prior to CED dasatinib compared to the CED dasatinib. However, tumor apoptosis was the highest in the pretreatment group (P < .001). Correspondingly, median OS was longer in the pretreatment group (49 d) than the dasatinib alone group (39 d) and no treatment controls (31.5 d, P = .0305).
conclusionABC transporter inhibition plus dexamethasone enhances the efficacy of CED dasatinib, resulting in enhanced tumor cellular apoptosis and improved survival in H3.3K27M mutant DIPG.
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