ReviewCancers2023
Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance.
Review in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- First-line immune checkpoint inhibitor plus anti-angiogenic therapy for advanced renal cell carcinoma: a meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2026Pooled it
- Identification of novel HIF2α inhibitors: a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Targeting p300/CBP destabilizes HIF-2α and suppresses tumor growth in cell and animal models of clear cell renal cell carcinoma.Cancer letters · 2026Article
- ReducedTranslational andrology and urology · 2026Article
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- Nutraceuticals in Uro-Oncology: A Structured Expert Review and Precision-Oriented Framework.Nutrients · 2026Review
- Expression of ABCB1, ABCB5, and ABCG2 Transporters in Human Renal Cell Carcinoma and Their Underlying Signaling Pathways.Current issues in molecular biology · 2026Article
- CYTH4 Facilitates Renal Cell Carcinoma via Enhancing Proliferation and Likely Immune Evasion.Biomolecules · 2026Article
- Natural Products in Clear Cell Renal Cell Carcinoma: Rewiring the VHL-HIF Axis, Metabolic Plasticity, and Tumor-Immune Interactions.International journal of molecular sciences · 2026Review
- Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrated Transcriptomic Analysis Identifies a Six-Gene Prognostic Signature, RNA Editing Derived Neoantigens, and miRNA Regulatory Networks in Renal Cell Carcinoma.Iranian journal of medical sciences · 2026Article
- Article
- Efferocytosis-related gene PLG in prognosis, immune correlation, and contribution to malignant behavior in vitro and in vivo of clear cell renal cell carcinoma.Scientific reports · 2026Article
- IBSP Promotes Clear Cell Renal Cell Carcinoma Progression Through the PI3 K/AKT Pathway.Biochemical genetics · 2026Article
- CXCR4, CXCR7 and PBRM1 are responsible for everolimus and cabozantinib resistance in human renal cancer cells.Cell death discovery · 2026Article
- Review
- Review
- Tumor microenvironment-driven drug resistance in urologic cancers: mechanisms and therapeutic targets.Genes & genomics · 2026Review
- First-Line Treatment Strategies in IMDC Favourable-Risk Metastatic Clear Cell Renal Cell Carcinoma.Oncology research · 2026Review
- Promoter Hypermethylation-Driven NPHS2 Silencing Promotes Immune Escape and Sunitinib Resistance in Clear Cell Renal Cell Carcinoma.Oncology research · 2026Article
6 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
3 authors at 1 institution in 1 country.
Funding
Abstract
The clear cell variant of renal cell carcinoma (ccRCC) is the most common renal epithelial malignancy and responsible for most of the deaths from kidney cancer. Patients carrying inactivating mutations in the Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several types of tumors including ccRCC. Normally, the Hypoxia Inducible Factor alpha (HIF-α) subunits of the HIF heterodimeric transcription factor complex are regulated by oxygen-dependent prolyl-hydroxylation, VHL-mediated ubiquitination and proteasomal degradation. Loss of pVHL function results in elevated levels of HIF-α due to increased stability, leading to RCC progression. While HIF-1α acts as a tumor suppressor, HIF-2α promotes oncogenic potential by driving tumor progression and metastasis through activation of hypoxia-sensitive signaling pathways and overexpression of HIF-2α target genes. One strategy to suppress ccRCC aggressiveness is directed at inhibition of HIF-2α and the associated molecular pathways leading to cell proliferation, angiogenesis, and metastasis. Indeed, clinical and pre-clinical data demonstrated the effectiveness of HIF-2α targeted therapy in attenuating ccRCC progression. This review focuses on the signaling pathways and the involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer oncogenic potential downstream of the VHL-HIF-2α signaling axis in ccRCC. Discussed as well are current treatment options (including receptor tyrosine kinase inhibitors such as sunitinib), the medical challenges (high prevalence of metastasis at the time of diagnosis, refractory nature of advanced disease to current treatment options), scientific challenges and future directions.
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.