Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2013
The role of aberrant VHL/HIF pathway elements in predicting clinical outcome to pazopanib therapy in patients with metastatic clear-cell renal cell carcinoma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 4 of them syntheses that pooled it.
What it found
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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
51 citing papers in PubMed, 4 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- A 23-year bibliometric analysis of the development of global research on hereditary renal carcinoma.Frontiers in oncology · 2024Pooled it
- Clinicopathologic Significance ofInternational journal of molecular sciences · 2018Pooled it
- Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.Oncotarget · 2017Pooled it
- Pooled it
- Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial.The Lancet. Oncology · 2018Trial
- Lysyl oxidase drives ccRCC progression by coordinating HIF-2α transcription program with tumor microenvironment.bioRxiv : the preprint server for biology · 2026Article
- Design and Synthesis of Bendamustine-Carbonic Anhydrase Inhibitors with Antiproliferative Effects in Clear Cell Renal Cell Carcinoma.Journal of medicinal chemistry · 2026Article
- Immune Escape in Renal Cell Carcinoma: Latest Research and Treatment Strategies.International journal of molecular sciences · 2026Review
- Short and Long Non-Coding RNAs in Renal Cell Carcinoma.Non-coding RNA · 2026Review
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- Dual loss of VHL and RASSF1A enhances tumorigenicity in clear cell renal cancer.Frontiers in oncology · 2026Article
- Targeting the Adenosine A2A Receptor as a Novel Therapeutic Approach for Renal Cell Carcinoma: Mechanisms and Clinical Trial Review.Pharmaceutics · 2024Review
- Review
- The Use of Integrated Molecular Testing in the Assessment and Management of Pancreatic Cysts.Current gastroenterology reports · 2023Review
- Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies.Cancers · 2022Review
- Precision Medicine: An Optimal Approach to Patient Care in Renal Cell Carcinoma.Frontiers in medicine · 2022Review
- Biomarkers in renal cell carcinoma: Are we there yet?Asian journal of urology · 2021Review
- Comprehensive Genomic Landscape in Chinese Clear Cell Renal Cell Carcinoma Patients.Frontiers in oncology · 2021Article
- The kinesin motor protein KIF4A as a potential therapeutic target in renal cell carcinoma.Investigational new drugs · 2020Article
- Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation.Journal of experimental & clinical cancer research : CR · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
purposeInactivation of von Hippel-Lindau (VHL) gene in clear-cell renal cell carcinoma (RCC) leads to increased levels of hypoxia-inducible factors (HIF) and overexpression of HIF target genes, such as VEGF and others. VEGF-targeted agents are standard in advanced clear-cell RCC but biomarkers of activity are lacking. EXPERIMENTAL
designWe analyzed tumor tissue samples from metastatic clear-cell RCC patients who received pazopanib as part of clinical trial VEG102616. We evaluated several components of the VHL/HIF pathway: VHL gene inactivation (mutation and/or methylation), HIF-1α and HIF-2α immunohistochemistry staining, and HIF-1α transcriptional signature. We evaluated the association of these biomarkers with best overall response rate (ORR) and progression-free survival (PFS) to pazopanib, a standard first-line VEGF-targeted agent.
resultsThe VEG102616 trial enrolled 225 patients, from whom 78 samples were available for tumor DNA extraction. Of these, 70 patients had VHL mutation or methylation. VHL gene status did not correlate with ORR or PFS. Similarly, HIF-1α (65 samples) and HIF-2α (66 samples) protein levels (high vs. low) did not correlate with ORR or PFS to pazopanib. The HIF-1α transcriptional signature (46 samples) was enriched in tumors expressing high HIF-1α levels. However, the HIF-1α gene expression signature was not associated with clinical outcome to pazopanib.
conclusionsIn patients with advanced clear-cell RCC, several potential biomarkers along the VHL/HIF-1α/HIF-2α axis were not found to be predictive for pazopanib activity. Additional efforts must continue to identify biomarkers associated with clinical outcome to VEGF-targeted agents in metastatic RCC.
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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.