ArticleNature communications2017
Loss of PBRM1 rescues VHL dependent replication stress to promote renal carcinogenesis.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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.
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Who cites it
77 citing papers in PubMed, 100 citations in OpenAlex.
- A Phase 1b/2 Study of Talazoparib and Axitinib in Patients with Advanced Clear-cell Renal Cell Carcinoma.European urology oncology · 2025Trial
- A Phase 2 Trial of Talazoparib and Avelumab in Genomically Defined Metastatic Kidney Cancer.European urology oncology · 2024Trial
- PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer.Science advances · 2026Article
- Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- Essential genetic mutations impair DNA damage repair and modulate tumor immune microenvironment in ccRCC.MedScience · 2026Review
- CXCR4, CXCR7 and PBRM1 are responsible for everolimus and cabozantinib resistance in human renal cancer cells.Cell death discovery · 2026Article
- Disulfidptosis induced by intermittent fasting and metformin enhances the efficacy of anti-PD-1 therapy in renal cancer.Cell communication and signaling : CCS · 2026Article
- Implications for clinical prognosis and target discovery of the SWI/SNF complex in genitourinary tumors.Discover oncology · 2026Review
- The bacterial MRE11-RAD50 and DNA2-WRN homologs process replication forks at distinct and separate loci on the chromosome.FEBS letters · 2026Article
- The expression, regulation, and function of human endogenous retroviruses in genitourinary cancers.Cell death discovery · 2025Review
- Cytosolic DNA and intracellular CaDNA repair · 2025Review
- Characterisation of an autochthonous mouse ccRCC model of immune checkpoint inhibitor therapy resistance.Scientific reports · 2025Article
- Clear cell renal carcinoma essentially requires CDKL3 for oncogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma.Journal of biomedical science · 2025Review
- PBRM1 deficiency enhances PD1 immunotherapeutic sensitivity via chromosomal accessibility in colorectal cancer.Theranostics · 2025Article
- Toward a CRISPR-based mouse model ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- VHL loss enhances antitumor immunity by activating the anti-viral DNA-sensing pathway.iScience · 2024Article
- Stage IA papillary and chromophobe renal cell carcinoma: effectiveness of cryoablation and partial nephrectomy.Insights into imaging · 2024Article
- Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type-Specific and Time-Resolved Responses to Vhl Inactivation in the Kidney.Cancer research · 2024Article
- Unveiling the hidden role of disulfidptosis in kidney renal clear cell carcinoma: a prognostic signature for personalized treatment.Apoptosis : an international journal on programmed cell death · 2024Article
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
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Inactivation of the VHL (Von Hippel Lindau) tumour suppressor has long been recognised as necessary for the pathogenesis of clear cell renal cancer (ccRCC); however, the molecular mechanisms underlying transformation and the requirement for additional genetic hits remain unclear. Here, we show that loss of VHL alone results in DNA replication stress and damage accumulation, effects that constrain cellular growth and transformation. By contrast, concomitant loss of the chromatin remodelling factor PBRM1 (mutated in 40% of ccRCC) rescues VHL-induced replication stress, maintaining cellular fitness and allowing proliferation. In line with these data we demonstrate that combined deletion of Vhl and Pbrm1 in the mouse kidney is sufficient for the development of fully-penetrant, multifocal carcinomas, closely mimicking human ccRCC. Our results illustrate how VHL and PBRM1 co-operate to drive renal transformation and uncover replication stress as an underlying vulnerability of all VHL mutated renal cancers that could be therapeutically exploited.
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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.