ArticleScience translational medicine2018
Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 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
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Effects of exercise on angiogenesis biomarkers in cancer patients: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Oxidized Lipoproteins Promote Resistance to Cancer Immunotherapy Independent of Patient Obesity.Cancer immunology research · 2021Trial
- Effect of Metformin on Breast Density in Overweight/Obese Premenopausal Women.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Trial
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- ADAMTS6 Promotes Angiogenesis and Tumor Growth in Gastric Carcinoma.Biochemical genetics · 2026Article
- Understanding the Interplay Between Obesity and Cancer: From Mechanisms to Therapeutic Opportunities.Cancers · 2026Review
- Review
- Adipocytes as Orchestrators of Multimodal Cancer Therapy Resistance.Biomolecules & therapeutics · 2026Review
- Review
- Vascular abnormalization confers tumor resistance to antiangiogenic therapy via downregulating angiostatic factors.Breast cancer research : BCR · 2026Article
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- The impact of chronic comorbidities on cancer immunoediting: challenges and opportunities for immunotherapies.Frontiers in immunology · 2026Review
- The Role of Angiogenesis in Breast Cancer and Obesity: Unravelling the Connection.International journal of breast cancer · 2026Review
- VEGF-Leptin Crosstalk in Breast and Ovarian Cancer: Drivers of Angiogenesis and Progression.Cancer management and research · 2026Review
- From mechanisms to management: Early detection and improved treatment of MASLD and its related hepatocellular carcinoma.Hepatology communications · 2025Review
- GLP-1 receptor agonists and cancer: current clinical evidence and translational opportunities for preclinical research.The Journal of clinical investigation · 2025Review
- Trends and projections of global gynaecological cancer burden: age-period-cohort insights from Global Burden of Disease 2021.BMC women's health · 2025Article
- Adipocyte-derived IL6 and triple-negative breast cancer cell-derived CXCL1 co-activate STAT3/NF-κB pathway to mediate the crosstalk between adipocytes and triple-negative breast cancer cells.Cell death discovery · 2025Article
- Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
25 authors at 2 institutions in 5 countries.
Funding
Abstract
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment. Mouse models revealed that obesity impairs the effects of anti-VEGF on angiogenesis, tumor growth, and metastasis. In one murine BC model, obesity was associated with increased IL-6 production from adipocytes and myeloid cells within tumors. IL-6 blockade abrogated the obesity-induced resistance to anti-VEGF therapy in primary and metastatic sites by directly affecting tumor cell proliferation, normalizing tumor vasculature, alleviating hypoxia, and reducing immunosuppression. Similarly, in a second mouse model, where obesity was associated with increased FGF-2, normalization of FGF-2 expression by metformin or specific FGF receptor inhibition decreased vessel density and restored tumor sensitivity to anti-VEGF therapy in obese mice. Collectively, our data indicate that obesity fuels BC resistance to anti-VEGF therapy via the production of inflammatory and angiogenic factors.
Indexed as
Identifiers
What OpenQuestion holds
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.