ArticleThe Journal of clinical investigation2011
Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
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- Gefitinib Plus BevacizumabIn vivo (Athens, Greece)Trial
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- Exosomes derived from M2 macrophage promote HUVECs proliferation, migration and tube formation in vitro.Scientific reports · 2025Article
- "Brake" and "accelerator": revisiting tumor cell direct responses and the paradox of aggression in anti-VEGF therapy.Frontiers in immunology · 2025Review
- Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024Review
- Effects of neratinib on angiogenesis and the early stage of the embryo using chicken embryo as a model.Biomolecules & biomedicine · 2024Article
- ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy.Nature metabolism · 2023Article
- Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors.International journal of molecular sciences · 2023Review
- Molecular Mechanisms and Future Implications of VEGF/VEGFR in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Targeting vascular normalization: a promising strategy to improve immune-vascular crosstalk in cancer immunotherapy.Frontiers in immunology · 2023Review
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- CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases.Science China. Life sciences · 2022Article
- Article
- Pharmacological inhibition of epidermal growth factor receptor attenuates intracranial aneurysm formation by modulating the phenotype of vascular smooth muscle cells.CNS neuroscience & therapeutics · 2022Article
- The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment.Frontiers in immunology · 2022Review
- Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment.Frontiers in cell and developmental biology · 2022Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Angiogenesis is critical for tumor growth and metastasis, and several inhibitors of angiogenesis are currently in clinical use for the treatment of cancer. However, not all patients benefit from antiangiogenic therapy, and those tumors that initially respond to treatment ultimately become resistant. The mechanisms underlying this, and the relative contributions of tumor cells and stroma to resistance, are not completely understood. Here, using species-specific profiling of mouse xenograft models of human lung adenocarcinoma, we have shown that gene expression changes associated with acquired resistance to the VEGF inhibitor bevacizumab occurred predominantly in stromal and not tumor cells. In particular, components of the EGFR and FGFR pathways were upregulated in stroma, but not in tumor cells. Increased activated EGFR was detected on pericytes of xenografts that acquired resistance and on endothelium of tumors with relative primary resistance. Acquired resistance was associated with a pattern of pericyte-covered, normalized revascularization, whereas tortuous, uncovered vessels were observed in relative primary resistance. Importantly, dual targeting of the VEGF and EGFR pathways reduced pericyte coverage and increased progression-free survival. These findings demonstrated that alterations in tumor stromal pathways, including the EGFR and FGFR pathways, are associated with, and may contribute to, resistance to VEGF inhibitors and that targeting these pathways may improve therapeutic efficacy. Understanding stromal signaling may be critical for developing biomarkers for angiogenesis inhibitors and improving combination regimens.
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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.