ArticleCancer discovery2012
Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors.
Article in Cancer discovery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06535737 (A Phase 2, Single Arm Study of Cabozantinib in Patients With Hepatocellular Carcinoma Who Have Received Prior Atezolizumab and Bevacizumab), which is not on this map. Cited by 208 papers, 3 of them syntheses 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.
A Phase 2, Single Arm Study of Cabozantinib in Patients With Hepatocellular Carcinoma Who Have Received Prior Atezolizumab and Bevacizumab
Who cites it
208 citing papers in PubMed, 3 syntheses or guidelines pooled it, 414 citations in OpenAlex.
- Evaluation of translational potential of mRNA vaccine candidate antigens for pancreatic cancer: a systematic review based on clinical evidence and stratified prioritization strategies.Frontiers in immunology · 2026Pooled it
- Cabozantinib for different endocrine tumours: killing two birds with one stone. A systematic review of the literature.Endocrine · 2024Pooled it
- Efficacy and Safety of Epidermal Growth Factor Receptor (EGFR) Inhibitors Plus Antiangiogenic Agents as First-Line Treatments for Patients With AdvancedFrontiers in oncology · 2020Pooled it
- Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors.The New England journal of medicine · 2025Trial
- A Phase Ib/II Study of Ramucirumab in Combination with Emibetuzumab in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.The New England journal of medicine · 2018Trial
- Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.The oncologist · 2018Trial
- Phase II study of single-agent cabozantinib in patients with recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer (NRG-GY001).Gynecologic oncology · 2018Trial
- Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma.British journal of cancer · 2017Trial
- A phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer.Investigational new drugs · 2016Trial
- Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study.Breast cancer research and treatment · 2016Trial
- Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial.Journal of translational medicine · 2016Trial
- Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.The New England journal of medicine · 2015Trial
- Cediranib for metastatic alveolar soft part sarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- Article
- CD93 blockade overcomes sunitinib resistance in pancreatic neuroendocrine tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Decoding Pancreatic Neuroendocrine Tumors: Molecular Profiles, Biomarkers, and Pathways to Personalized Therapy.International journal of molecular sciences · 2025Review
- Vascular Endothelial Growth Factor Receptors in the Vascularization of Pancreatic Tumors: Implications for Prognosis and Therapy.Current issues in molecular biology · 2025Review
- Bioactive Products Targeting C-Met As Potential Antitumour Drugs.Anti-cancer agents in medicinal chemistry · 2025Review
148 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledInvasion and metastasis increase after the inhibition of VEGF signaling in some preclinical tumor models. In the present study we asked whether selective VEGF inhibition is sufficient to increase invasion and metastasis and whether selective c-Met inhibition is sufficient to block this effect. Treatment of pancreatic neuroendocrine tumors in RIP-Tag2 mice with a neutralizing anti-VEGF antibody reduced tumor burden but increased tumor hypoxia, hypoxia-inducible factor-1α, and c-Met activation and also increased invasion and metastasis. However, invasion and metastasis were reduced by concurrent inhibition of c-Met by PF-04217903 or PF-02341066 (crizotinib). A similar benefit was found in orthotopic Panc-1 pancreatic carcinomas treated with sunitinib plus PF-04217903 and in RIP-Tag2 tumors treated with XL184 (cabozantinib), which simultaneously blocks VEGF and c-Met signaling. These findings document that invasion and metastasis are promoted by selective inhibition of VEGF signaling and can be reduced by the concurrent inhibition of c-Met. SIGNIFICANCE: This report examines the mechanism of increased tumor aggressiveness after anti-VEGF therapy and presents evidence for roles of vascular pruning, hypoxia, and c-Met activation. The results show that simultaneous inhibition of c-Met and VEGF signaling not only slows tumor growth but also reduces invasion and metastasis.
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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.