Trial reportPloS one2013
The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer.
Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?Cancer biology & therapy · 2015Pooled it
- Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
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- Vascular endothelial growth factor D expression is a potential biomarker of bevacizumab benefit in colorectal cancer.British journal of cancer · 2015Trial
- Angiogenic Doping: Plausible Yet Difficult to Detect.Sports medicine (Auckland, N.Z.) · 2026Review
- Advancing Systemic Treatment beyond First Line for Advanced Hepatocellular Carcinoma.Current oncology reports · 2026Review
- Systemic targeting of aberrant neovascular tufts using trehalose-dendrimer nanocarriers for the treatment of proliferative retinopathies.Theranostics · 2026Article
- Prolonged exposure to axitinib alters the molecular profile of Caki-2 renal cell carcinoma cells.Molecular and clinical oncology · 2025Article
- Predicting Survival in Bevacizumab-Treated Colorectal Cancer: Personalized Mathematical Models Based on Clinical and Angiogenic Biomarkers.International journal of molecular sciences · 2025Article
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- Targeting the tumour vasculature: from vessel destruction to promotion.Nature reviews. Cancer · 2024Review
- Vascular Endothelial Growth Factor C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular Age-Related Macular Degeneration: A Narrative Review.Ophthalmology and therapy · 2024Review
- Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies.Stem cells international · 2024Review
- Current Status of Angiogenesis Inhibitors as Second-Line Treatment for Unresectable Colorectal Cancer.Cancers · 2023Review
- Role of plasma angiogenesis factors in the efficacy of first-line chemotherapy combined with biologics in RAS wild-type metastatic colorectal cancer: Results from the GI-SCREEN CRC-Ukit study.Cancer medicine · 2023Observational
- Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors.International journal of molecular sciences · 2023Review
- Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World journal of gastroenterology · 2023Review
- Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration.Journal of translational medicine · 2023Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCirculating angiogenic factors are altered in patients with mCRC receiving bevacizumab. Evaluation of alterations in levels of VEGF ligands may provide insights into possible resistance mechanisms.
methodsPlGF, VEGF-A, VEGF-C, and VEGF-D were measured from two cohorts of patients. Sequential plasma samples were obtained from a discovery cohort of 42 patients treated with chemotherapy and bevacizumab. A validation cohort included plasma samples from a cross-sectional of 403 patients prior to chemotherapy, or after progression on a regimen with or without bevacizumab.
resultsIn the discovery cohort, VEGF-C was increased prior to progression and at progression (+49% and +95%, respectively, p<0.01), consistent with previously reported elevations in PlGF. Levels of VEGF-D were increased (+23%) at progression (p=0.05). In the validation cohort, samples obtained from patients after progression on a regimen with bevacizumab had higher levels of PlGF and VEGF-D (+43% and +6%, p=0.02, p=0.01, respectively) compared to untreated patients, but failed to validate the increase in VEGF-C seen in the first cohort. Patients who progressed on chemotherapy with bevacizumab had significantly elevated levels of PlGF (+88%) but not VEGF-C and VEGF-D compared to patients treated with chemotherapy alone. Elevations of PlGF and VEGF-D appeared transient and returned to baseline with a half-life of 6 weeks.
conclusionsIncreases in PlGF and VEGF-D were observed after progression on chemotherapy with bevacizumab. These changes appear to be reversible after discontinuing therapy. These ligands are associated with resistance to bevacizumab-containing chemotherapy in mCRC, but causation remains to be established.
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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.