ArticleNeuro-oncology advances
Preclinical and clinical investigation of intratumoral chemotherapy pharmacokinetics in DIPG using gemcitabine.
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 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- PRMT5 Maintains Tumor Stem Cells to Promote Pediatric High-Grade Glioma Tumorigenesis.Molecular cancer research : MCR · 2025Article
- Targeting Intracranial Tumours with a Combination of RNA and Chemotherapy.Pharmaceutics · 2024Article
- Diffuse intrinsic pontine glioma (DIPG): A review of current and emerging treatment strategies.Cancer letters · 2024Review
- Spatial transcriptomic analysis of Sonic hedgehog medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition.Genome medicine · 2023Article
- A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease.Frontiers in oncology · 2023Article
- Current perspectives on diffuse midline glioma and a different role for the immune microenvironment compared to glioblastoma.Journal of neuroinflammation · 2022Review
- Leveraging Open Science Drug Development for PET: Preliminary Neuroimaging ofACS medicinal chemistry letters · 2021Article
- Review
- MRI-guided focused ultrasound blood-brain barrier opening increases drug delivery and efficacy in a diffuse midline glioma mouse model.Neuro-oncology advancesArticle
- Pediatric diffuse midline glioma: Understanding the mechanisms and assessing the next generation of personalized therapeutics.Neuro-oncology advancesReview
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundHundreds of systemic chemotherapy trials in diffuse intrinsic pontine glioma (DIPG) have not improved survival, potentially due to lack of intratumoral penetration, which has not previously been assessed in humans.
methodsWe used gemcitabine as a model agent to assess DIPG intratumoral pharmacokinetics (PK) using mass spectrometry.
resultsIn a phase 0 clinical trial of i.v. gemcitabine prior to biopsy in children newly diagnosed with DIPG by MRI, mean concentration in 4 biopsy cores in patient 1 (H3K27M diffuse midline glioma) was 7.65 µM. These compare favorably to levels for patient 2 (mean 3.85 µM, found to have an H3K27-wildtype low-grade glioma on histology), and from a similar study in adult glioblastoma (adjusted mean 3.48 µM). In orthotopic patient-derived xenograft (PDX) models of DIPG and H3K27M-wildtype pediatric glioblastoma, gemcitabine levels and clearance were similar in tumor, pons, and cortex and did not depend on H3K27 mutation status or tumor location. Normalized gemcitabine levels were similar in patient 1 and the DIPG PDX.
conclusionsThese findings, while limited to one agent, provide preliminary evidence for the hypotheses that lack of intratumoral penetration is not why systemic chemotherapy has failed in DIPG, and orthotopic PDX models can adequately model intratumoral PK in human DIPG.
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