ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Angiopoietin-2 interferes with anti-VEGFR2-induced vessel normalization and survival benefit in mice bearing gliomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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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.
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Who cites it
78 citing papers in PubMed, 136 citations in OpenAlex.
- Systemic counterregulatory response of angiopoietin-2 after aflibercept therapy for nAMD: a potential escape mechanism.Acta ophthalmologica · 2021Trial
- Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins.Molecular neurobiology · 2025Article
- Bispecific Antibodies in Glioblastoma: Mechanistic Advances, Delivery Innovations, and Translational Challenges in Overcoming Immune Escape.International journal of medical sciences · 2025Review
- Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.Neuro-oncology · 2024Article
- A bibliometric analysis of the research landscape on vascular normalization in cancer.Heliyon · 2024Article
- Short Term Effect of Pre-Operative Anti-VEGF on Angiogenic and Fibrotic Profile of Fibrovascular Membranes of Proliferative Diabetic Retinopathy.Investigative ophthalmology & visual science · 2024Article
- Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies.Stem cells international · 2024Review
- Tumor Niches: Perspectives for Targeted Therapies in Glioblastoma.Antioxidants & redox signaling · 2023Review
- Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.Acta pharmaceutica Sinica. B · 2023Review
- The strange Microenvironment of Glioblastoma.Revue neurologique · 2023Review
- Shaping the brain vasculature in development and disease in the single-cell era.Nature reviews. Neuroscience · 2023Review
- Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity.International journal of molecular sciences · 2023Review
- Novel fusion protein PK5-RL-Gal-3C inhibits hepatocellular carcinoma via anti-angiogenesis and cytotoxicity.BMC cancer · 2023Article
- Do animal models of brain tumors replicate human peritumoral edema? a systematic literature search.Journal of neuro-oncology · 2023Review
- An agonistic anti-Tie2 antibody suppresses the normal-to-tumor vascular transition in the glioblastoma invasion zone.Experimental & molecular medicine · 2023Article
- Predictive potential of angiopoietin-2 in a mCRC subpopulation treated with vanucizumab in the McCAVE trial.Frontiers in oncology · 2023Article
- Targeting vascular normalization: a promising strategy to improve immune-vascular crosstalk in cancer immunotherapy.Frontiers in immunology · 2023Review
- Anti-angiogenic therapy in ovarian cancer: Current understandings and prospects of precision medicine.Frontiers in pharmacology · 2023Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeIn brain tumors, cerebral edema is a significant source of morbidity and mortality. Recent studies have shown that inhibition of vascular endothelial growth factor (VEGF) signaling induces transient vascular normalization and reduces cerebral edema, resulting in a modest survival benefit in glioblastoma patients. During anti-VEGF treatment, circulating levels of angiopoietin (Ang)-2 remained high after an initial minor reduction. It is not known, however, whether Ang-2 can modulate anti-VEGF treatment of glioblastoma. Here, we used an orthotopic glioma model to test the hypothesis that Ang-2 is an additional target for improving the efficacy of current anti-VEGF therapies in glioma patients. EXPERIMENTAL
designTo recapitulate high levels of Ang-2 in glioblastoma patients during anti-VEGF treatment, Ang-2 was ectopically expressed in U87 glioma cells. Animal survival and tumor growth were assessed to determine the effects of Ang-2 and anti-VEGF receptor 2 (VEGFR2) treatment. We also monitored morphologic and functional vascular changes using multiphoton laser scanning microscopy and immunohistochemistry.
resultsEctopic expression of Ang-2 had no effect on vascular permeability, tumor growth, or survival, although it resulted in higher vascular density, with dilated vessels and reduced mural cell coverage. On the other hand, when combined with anti-VEGFR2 treatment, Ang-2 destabilized vessels without affecting vessel regression and compromised the survival benefit of VEGFR2 inhibition by increasing vascular permeability. VEGFR2 inhibition normalized tumor vasculature whereas ectopic expression of Ang-2 diminished the beneficial effects of VEGFR2 blockade by inhibiting vessel normalization.
conclusionCancer treatment regimens combining anti-VEGF and anti-Ang-2 agents may be an effective strategy to improve the efficacy of current anti-VEGF therapies.
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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.