ArticleMolecular cancer2023
Local delivery of hrBMP4 as an anticancer therapy in patients with recurrent glioblastoma: a first-in-human phase 1 dose escalation trial.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02869243 (A Dose Escalation Phase I Study Of Human- Recombinant Bone Morphogenetic Protein 4 Administrated Via Convection-Enhanced Delivery In Patients With Progressive And/Or Multiple Recurrent Glioblastoma Multiforme), which is not on this map. Cited by 20 papers.
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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.
A Dose Escalation Phase I Study Of Human- Recombinant Bone Morphogenetic Protein 4 Administrated Via Convection-Enhanced Delivery In Patients With Progressive And/Or Multiple Recurrent Glioblastoma Multiforme
Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses.bioRxiv : the preprint server for biology · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- The stem cell within the vessel wall: multipotent pericytes modulating β-cell function and diabetic complications.Stem cell research & therapy · 2025Review
- Virtual Clinical Trials of BMP4 Differentiation Therapy: Digital Twins to Aid Successful Glioblastoma Trial Design.bioRxiv : the preprint server for biology · 2025Article
- Transcriptomic Comparisons of Somatic and Cancer Stem Cells.Biomedicines · 2025Review
- Targeting the glioblastoma resection margin with locoregional nanotechnologies.Nature reviews. Clinical oncology · 2025Review
- p21-Dependent Senescence Induction by BMP4 Renders Glioblastoma Cells Vulnerable to Senolytics.International journal of molecular sciences · 2025Article
- A phase I study of convection-enhanced delivery (CED) of liposomal-irinotecan using real-time magnetic resonance imaging in patients with recurrent high-grade glioma.Journal of neuro-oncology · 2025Article
- Regenerative Glycopeptide Scaffolds Enhance BMP-4 Activity To Treat Pediatric Glioma.Regenerative engineering and translational medicine · 2025Article
- Device-assisted strategies for drug delivery across the blood-brain barrier to treat glioblastoma.Communications materials · 2025Review
- Recent Advances in the Delivery of Bone Morphogenetic Proteins for Targeting Glioma: An Updated Review.International journal of nanomedicine · 2025Review
- Therapeutic potential and impact of nanoengineered patient-derived mesenchymal stem cells in a murine resection and recurrence model of human glioblastoma.Bioengineering & translational medicine · 2024Article
- BMP4 and Temozolomide Synergize in the Majority of Patient-Derived Glioblastoma Cultures.International journal of molecular sciences · 2024Article
- Local therapy in glioma: An evolving paradigm from history to horizons (Review).Oncology letters · 2024Review
- A Review of Therapeutic Agents Given by Convection-Enhanced Delivery for Adult Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Bone Morphogenetic Protein Signaling Agonist SB4 (BMPSB4) Inhibits Corticotroph Pituitary Neuroendocrine Tumors by Activation of Autophagy via a BMP4/SMADs-Dependent Pathway.ACS pharmacology & translational science · 2024Article
- Bone Morphogenic Proteins in Pediatric Diffuse Midline Gliomas: How to Make New Out of Old?International journal of molecular sciences · 2024Review
- Adjuvant convection-enhanced delivery for the treatment of brain tumors.Journal of neuro-oncology · 2024Review
- Review
- PNOC009: Convection-enhanced delivery of liposomal irinotecan in patients with newly diagnosed diffuse intrinsic pontine glioma.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) - an inhibitory regulator of cancer stem cells (CSCs) - in recurrent glioblastoma.
methodsIn a 3 + 3 dose escalation design, over four to six days, fifteen recurrent glioblastoma patients received, by CED, one of five doses of hrBMP4 ranging from 0·5 to 18 mg. Patients were followed by periodic physical, neurological, blood testing, magnetic resonance imaging (MRI) and quality of life evaluations. The primary objective of this first-in-human study was to determine the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of hrBMP4. Secondary objectives were to assess potential efficacy and systemic exposure to hrBMP4 upon intracerebral infusion.
resultsIntra- and peritumoral infusion of hrBMP4 was safe and well-tolerated. We observed no serious adverse events related to this drug. Neither MTD nor DLT were reached. Three patients had increased hrBMP4 serum levels at the end of infusion, which normalized within 4 weeks, without sign of toxicity. One patient showed partial response and two patients a complete (local) tumor response, which was maintained until the most recent follow-up, 57 and 30 months post-hrBMP4. Tumor growth was inhibited in areas permeated by hrBMP4.
conclusionLocal delivery of hrBMP4 in and around recurring glioblastoma is safe and well-tolerated. Three patients responded to the treatment. A complete response and long-term survival occurred in two of them. This warrants further clinical studies on this novel treatment targeting glioblastoma CSCs.
trial registrationClinicaTrials.gov identifier: NCT02869243.
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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 Socratic graph.