ArticleJournal of neurosurgery2017
Combination therapy in a xenograft model of glioblastoma: enhancement of the antitumor activity of temozolomide by an MDM2 antagonist.
Article in Journal of neurosurgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Topotecan Synergizes with SP141 in the Management of Uveal Melanoma.bioRxiv : the preprint server for biology · 2026Article
- A Comprehensive Analysis of Natural Bioactive Molecules for the Treatment and Control of Glioblastoma Multiforme (GBM) Targeting Underlying Molecular Mechanism.Chemistry & biodiversity · 2026Review
- Key genes altered in glioblastoma based on bioinformatics (Review).Oncology letters · 2025Review
- Review
- Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models.Cancers · 2024Review
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- synNotch-programmed iPSC-derived NK cells usurp TIGIT and CD73 activities for glioblastoma therapy.Nature communications · 2024Article
- Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024Review
- MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2βcc in a p53-independent manner.Cell death & disease · 2024Article
- A New Drug Discovery Platform: Application to DNA Polymerase Eta and Apurinic/Apyrimidinic Endonuclease 1.International journal of molecular sciences · 2023Article
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- Understanding the molecular profiling of diffuse gliomas classification: A brief overview.Surgical neurology international · 2023Article
- Functional expression of CD73 on human natural killer cells.Cancer immunology, immunotherapy : CII · 2022Article
- Alterations in Molecular Profiles Affecting Glioblastoma Resistance to Radiochemotherapy: Where Does the Good Go?Cancers · 2022Review
- Article
- Pediatric versus adult high grade glioma: Immunotherapeutic and genomic considerations.Frontiers in immunology · 2022Review
- Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenicFrontiers in oncology · 2022Article
- Tumor-Associated Microglia/Macrophages as a Predictor for Survival in Glioblastoma and Temozolomide-Induced Changes in CXCR2 Signaling with New Resistance Overcoming Strategy by Combination Therapy.International journal of molecular sciences · 2021Article
- Development of CD133 Targeting Multi-Drug Polymer Micellar Nanoparticles for Glioblastoma - In Vitro Evaluation in Glioblastoma Stem Cells.Pharmaceutical research · 2021Article
- Combined inhibition of Ref-1 and STAT3 leads to synergistic tumour inhibition in multiple cancers using 3D and in vivo tumour co-culture models.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 3 countries.
Funding
Abstract
OBJECTIVE Improvement in treatment outcome for patients with glioblastoma multiforme (GBM) requires a multifaceted approach due to dysregulation of numerous signaling pathways. The murine double minute 2 (MDM2) protein may fulfill this requirement because it is involved in the regulation of growth, survival, and invasion. The objective of this study was to investigate the impact of modulating MDM2 function in combination with front-line temozolomide (TMZ) therapy in GBM. METHODS The combination of TMZ with the MDM2 protein-protein interaction inhibitor nutlin3a was evaluated for effects on cell growth, p53 pathway activation, expression of DNA repair proteins, and invasive properties. In vivo efficacy was assessed in xenograft models of human GBM. RESULTS In combination, TMZ/nutlin3a was additive to synergistic in decreasing growth of wild-type p53 GBM cells. Pharmacodynamic studies demonstrated that inhibition of cell growth following exposure to TMZ/nutlin3a correlated with: 1) activation of the p53 pathway, 2) downregulation of DNA repair proteins, 3) persistence of DNA damage, and 4) decreased invasion. Pharmacokinetic studies indicated that nutlin3a was detected in human intracranial tumor xenografts. To assess therapeutic potential, efficacy studies were conducted in a xenograft model of intracranial GBM by using GBM cells derived from a recurrent wild-type p53 GBM that is highly TMZ resistant (GBM10). Three 5-day cycles of TMZ/nutlin3a resulted in a significant increase in the survival of mice with GBM10 intracranial tumors compared with single-agent therapy. CONCLUSIONS Modulation of MDM2/p53-associated signaling pathways is a novel approach for decreasing TMZ resistance in GBM. To the authors' knowledge, this is the first study in a humanized intracranial patient-derived xenograft model to demonstrate the efficacy of combining front-line TMZ therapy and an inhibitor of MDM2 protein-protein interactions.
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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.