ArticleNeuro-oncology advances
Overcoming translational barriers in H3K27-altered diffuse midline glioma: Increasing the drug-tumor residence time.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
7 citing papers in PubMed, 5 citations in OpenAlex.
- Review
- Radiotherapy plus neoadjuvant and concomitant IL-13Rα2-directed immunotoxin therapy for diffuse intrinsic pontine glioma.Communications biology · 2026Article
- Enhanced Delivery of Aurora Kinase A Inhibitor Alisertib via Tumor-Targeting Immunoliposome Nanocomplex for Improved Treatment of Cancers Including Atypical Teratoid/Rhabdoid Tumor.International journal of nanomedicine · 2026Article
- Review
- How Much is Enough? Impact of Efflux Transporters on Drug delivery Leading to Efficacy in the Treatment of Brain Tumors.Pharmaceutical research · 2023Review
- Self-assembling polypeptide-drug conjugates as innovative therapeutic candidates for glioblastoma treatment by enhancing intracranial residence time.Neuro-oncology advancesArticle
- Bench-to-bedside investigations of H3 K27-altered diffuse midline glioma: drug targets and potential pharmacotherapies.Expert opinion on therapeutic targetsReview
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Background: H3K27-altered diffuse midline glioma (DMG) is the deadliest pediatric brain tumor; despite intensive research efforts, every clinical trial to date has failed. Is this because we are choosing the wrong drugs? Or are drug delivery and other pharmacokinetic variables at play? We hypothesize that the answer is likely a combination, where optimization may result in a much needed novel therapeutic approach. Methods: We used in vitro drug screening, patient samples, and shRNA knockdown models to identify an upregulated target in DMG. A single small molecule protein kinase inhibitor with translational potential was selected for systemic and direct, loco-regional delivery to patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM). Pharmacokinetic studies were conducted in non-tumor bearing rats. Results: Aurora kinase (AK) inhibitors demonstrated strong antitumor effects in DMG drug screens. Additional in vitro studies corroborated the importance of AK to DMG survival. Systemic delivery of alisertib showed promise in subcutaneous PDX but not intracranial GEMM and PDX models. Repeated loco-regional drug administration into the tumor through convection-enhanced delivery (CED) was equally inefficacious, and pharmacokinetic studies revealed rapid clearance of alisertib from the brain. In an effort to increase the drug to tumor residence time, continuous CED over 7 days improved drug retention in the rodent brainstem and significantly extended survival in both orthotopic PDXs and GEMMs. Conclusions: These studies provide evidence for increasing drug-tumor residence time of promising targeted therapies via extended CED as a valuable treatment strategy for DMG.
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Registered trials
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.