ArticleClinical & experimental metastasis2020
Nintedanib and a bi-specific anti-VEGF/Ang2 nanobody selectively prevent brain metastases of lung adenocarcinoma cells.
Article in Clinical & experimental metastasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.Frontiers in immunology · 2021Pooled it
- Nanobody-based targeted cancer therapy and immunotherapy: fear not the future.Acta pharmacologica Sinica · 2026Review
- Vascular Endothelial Growth Factor/Angiopoietin-2 Bispecific Antibody-Induced Vascular Normalization: From Basic Mechanisms to Therapeutic Applications in Breast Cancer.Immunity, inflammation and disease · 2026Review
- Voxel-accurate MRI-microscopy Correlation Enables AI-powered Prediction of Brain Disease States.Theranostics · 2026Article
- Spatial Cross-talk Modeling of the Tumor Microenvironment Identifies CCR5-Mediated Glia-to-Glia Signaling as a Key Regulator of Brain Metastatic Progression.Cancer research · 2025Article
- Cancer brain metastasis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Neurooncology: 2025 update.Free neuropathology · 2025Review
- Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.Neuro-oncology · 2024Article
- Thrombosis, brain metastasis formation, and the perivascular metastatic niche-Novel insights from the tumor microvascular circulation.Neuro-oncology · 2024Article
- Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Preclinical evaluation of the VEGF/Ang2 bispecific nanobody BI 836880 in nasopharyngeal carcinoma models.Investigational new drugs · 2023Article
- Article
- A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts.APL bioengineering · 2023Article
- Predictive potential of angiopoietin-2 in a mCRC subpopulation treated with vanucizumab in the McCAVE trial.Frontiers in oncology · 2023Article
- Disrupting cancer angiogenesis and immune checkpoint networks for improved tumor immunity.Seminars in cancer biology · 2022Review
- FOXA1 prevents nutrients deprivation induced autophagic cell death through inducing loss of imprinting of IGF2 in lung adenocarcinoma.Cell death & disease · 2022Article
- Novel Drugs with High Efficacy against Tumor Angiogenesis.International journal of molecular sciences · 2022Review
- VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment.International journal of biological sciences · 2022Review
- The microenvironment of brain metastases from solid tumors.Neuro-oncology advances · 2021Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain metastases (BM) are an ever-increasing challenge in oncology, threatening quality of life and survival of many cancer patients. The majority of BM originate from lung adenocarcinoma, and stage III patients have a risk of 40-50% to develop BM in the first years of disease onset. As therapeutic options are limited, prevention of their occurrence is an attractive concept. Here we investigated whether Nintedanib (BIBF 1120), a tyrosine kinase inhibitor (TKI) targeting the VEGF pathway approved for lung adenocarcinoma, and the dual anti-VEGF-A/Ang2 nanobody BI836880 have the potential to prevent BM formation. A mouse model of brain metastasis from lung adenocarcinoma was used in which tumor cells were injected intracardially. Metastases formation occurred inside and outside of the brain and was followed by MRI, IVIS, and immunohistochemistry. BM were reduced in volume and number by both Nintedanib and the dual anti-VEGF-A/Ang2 nanobody, which translated into improved survival. Both compounds were able to normalize cerebral blood vessels at the site of brain metastatic lesions. Extracranial metastases, however, were not reduced, and meningeal metastases only partially. Interestingly, unspecific control IgG also lead to brain vessel normalization and reduction of brain and meningeal metastases. This data indicates a brain-specific group effect of antiangiogenic compounds with respect to metastasis prevention, most likely by preventing an early angiogenic switch. Thus, Nintedanib and BI836880 are promising candidates for future BM preventive study concepts in lung adenocarcinoma patients.
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