ArticleOncotarget2014
Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Endothelial von Hippel-Lindau gene deletion causes abnormal blood and lymphatic vasculature through ectopic activation of the HIF-CXCR4 axis.Development (Cambridge, England) · 2026Article
- The role of CXC chemokines and receptors in breast cancer.Clinical and experimental medicine · 2025Review
- Extracellular vesicles and cancer stem cells: a deadly duo in tumor progression.Oncology reviews · 2024Review
- Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.Brain sciences · 2023Review
- The role of tumor microenvironment on cancer stem cell fate in solid tumors.Cell communication and signaling : CCS · 2023Review
- The prospect of tumor microenvironment-modulating therapeutical strategies.Frontiers in oncology · 2022Review
- VEGFR2 activity on myeloid cells mediates immune suppression in the tumor microenvironment.JCI insight · 2021Article
- At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer.Journal of leukocyte biology · 2021Review
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment.Journal of hematology & oncology · 2020Review
- Novel CXCR4 Inhibitor CPZ1344 Inhibits the Proliferation, Migration and Angiogenesis of Glioblastoma.Pathology oncology research : POR · 2020Article
- Cancer Stem Cells and Its Role in Angiogenesis and Vasculogenic Mimicry in Gastrointestinal Cancers.Frontiers in oncology · 2020Review
- Therapeutic Strategies Targeting Cancer Stem Cells and Their Microenvironment.Frontiers in oncology · 2019Review
- Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain.International journal of radiation oncology, biology, physics · 2018Article
- Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer.Frontiers in immunology · 2018Review
- Multifaceted C-X-C Chemokine Receptor 4 (CXCR4) Inhibition Interferes with Anti-Vascular Endothelial Growth Factor Therapy-Induced Glioma Dissemination.The American journal of pathology · 2017Article
- Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma.Journal of biological rhythms · 2017Article
- The Unexpected Roles of Aurora A Kinase in Gliobastoma Recurrences.Targeted oncology · 2017Review
- The brain-penetrating CXCR4 antagonist, PRX177561, increases the antitumor effects of bevacizumab and sunitinib in preclinical models of human glioblastoma.Journal of hematology & oncology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Glioblastoma recurrence involves the persistence of a subpopulation of cells with enhanced tumor-initiating capacity (TIC) that reside within the perivascular space, or niche (PVN). Anti-angiogenic therapies may prevent the formation of new PVN but have not prevented recurrence in clinical trials, suggesting they cannot abrogate TIC activity. We hypothesized that combining anti-angiogenic therapy with blockade of PVN function would have superior anti-tumor activity. We tested this hypothesis in an established intracranial xenograft model of GBM using a monoclonal antibody specific for murine and human VEGF (mcr84) and a Protein Epitope Mimetic (PEM) CXCR4 antagonist, POL5551. When doses of POL5551 were increased to overcome an mcr84-induced improvement in vascular barrier function, combinatorial therapy significantly inhibited intracranial tumor growth and improved survival. Anti-tumor activity was associated with significant changes in tumor cell proliferation and apoptosis, and a reduction in the numbers of perivascular cells expressing the TIC marker nestin. A direct effect on TICs was demonstrated for POL5551, but not mcr84, in three primary patient-derived GBM isolates. These findings indicate that targeting the structure and function of the PVN has superior anti-tumor effect and provide a strong rationale for clinical evaluation of POL5551 and Avastin in patients with GBM.
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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.