ArticleEMBO molecular medicine2016
Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed.
- Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.Cancer cell · 2018Trial
- Association between PLVAP downregulation and increased lymphocyte infiltration in newly diagnosed glioblastoma treated with bevacizumab.Brain tumor pathology · 2026Article
- Imaging biomarkers for detecting IDH mutations and monitoring response to novel targeted therapies: Current insights and future perspectives.Neuro-oncology · 2026Review
- Review
- Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance.Current pharmaceutical design · 2026Review
- Robust prediction of glioma prognosis by hypoxia-induced ferroptosis genes: VEGFA-XBP1 co-expression for salvage therapy.Cancer biology & therapy · 2025Article
- Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Glioblastoma at the crossroads: current understanding and future therapeutic horizons.Signal transduction and targeted therapy · 2025Review
- Colorectal Cancer: Current and Future Therapeutic Approaches and Related Technologies Addressing Multidrug Strategies Against Multiple Level Resistance Mechanisms.International journal of molecular sciences · 2025Review
- Breaking down physical barriers: strategies to improve lymphocyte infiltration for effective neoantigen-based therapies.Frontiers in immunology · 2025Review
- ICAM1-Mediated Endothelial Cells and Macrophage Interactions in Modulating GBM Malignant Transformation.Journal of inflammation research · 2025Article
- Bispecific Antibodies in Glioblastoma: Mechanistic Advances, Delivery Innovations, and Translational Challenges in Overcoming Immune Escape.International journal of medical sciences · 2025Review
- Pericytes in Glioblastoma: Hidden Regulators of Tumor Vasculature and Therapy Resistance.Cancers · 2024Review
- Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.Neuro-oncology · 2024Article
- Targeting drug resistance in glioblastoma (Review).International journal of oncology · 2024Review
- Milestones in tumor vascularization and its therapeutic targeting.Nature cancer · 2024Review
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- The ubiquitin-like protein FAT10 in hepatocellular carcinoma cells limits the efficacy of anti-VEGF therapy.Journal of advanced research · 2024Article
- Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment.Brain tumor pathology · 2024Article
- Novel specific anti-ESM1 antibodies overcome tumor bevacizumab resistance by suppressing angiogenesis and metastasis.Cancer science · 2023Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma multiforme (GBM) is treated by surgical resection followed by radiochemotherapy. Bevacizumab is commonly deployed for anti-angiogenic therapy of recurrent GBM; however, innate immune cells have been identified as instigators of resistance to bevacizumab treatment. We identified angiopoietin-2 (Ang-2) as a potential target in both naive and bevacizumab-treated glioblastoma. Ang-2 expression was absent in normal human brain endothelium, while the highest Ang-2 levels were observed in bevacizumab-treated GBM. In a murine GBM model, VEGF blockade resulted in endothelial upregulation of Ang-2, whereas the combined inhibition of VEGF and Ang-2 leads to extended survival, decreased vascular permeability, depletion of tumor-associated macrophages, improved pericyte coverage, and increased numbers of intratumoral T lymphocytes. CD206(+) (M2-like) macrophages were identified as potential novel targets following anti-angiogenic therapy. Our findings imply a novel role for endothelial cells in therapy resistance and identify endothelial cell/myeloid cell crosstalk mediated by Ang-2 as a potential resistance mechanism. Therefore, combining VEGF blockade with inhibition of Ang-2 may potentially overcome resistance to bevacizumab therapy.
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Registered trials
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