Evidence map›Paper›PMID 39707614›Full record

ArticleInternational journal of cancer2025

Exploiting NRF2-ARE pathway activation in papillary renal cell carcinoma.

Silvia Angori, Harini Lakshminarayanan, Amir Banaei-Esfahani, Katharina Mühlbauer, Hella Anna Bolck, Olli Kallioniemi, Vilja Pietiäinen, Peter Schraml, Holger Moch

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Article in International journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Silvia AngoriDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.ORCID 0000-0002-5823-3670
Harini LakshminarayananDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Amir Banaei-EsfahaniDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Katharina MühlbauerDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Hella Anna BolckDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.ORCID 0000-0001-5157-0490
Olli KallioniemiInstitute for Molecular Medicine Finland-FIMM, Helsinki Institute of Life Science-HiLIFE, University of Helsinki, Helsinki, Finland.
Vilja PietiäinenInstitute for Molecular Medicine Finland-FIMM, Helsinki Institute of Life Science-HiLIFE, University of Helsinki, Helsinki, Finland.
Peter SchramlDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Holger MochDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung S-87701-03-01Swiss Group for Clinical Cancer Research (SAKK) with AMGEN research grantUniversity Research Priority Program (URPP) in Translational Cancer Research
6 · The paper itself

Abstract

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype but has no indicated targeted treatments. MET inhibition may be a treatment for MET-driven pRCC, but there is a large group of non-MET-driven pRCC without targeted therapy. Activation of NRF2-ARE pathway has been suggested to be involved in pRCC. To study the relevance of the NRF2-ARE pathway, we characterized 60 pRCCs by copy number analysis and Whole Exome Sequencing. Because stabilisation of NRF2 results in enhanced expression of NQO1, a reductase that prevents production of reactive oxygen species, protein expression of NQO1 was analysed by immunohistochemistry (IHC) from tissue microarrays (TMAs) and by enzymatic activity assay. Finally, patient-derived pRCC cells (PDCs) were applied for drug profiling with 18 NRF2-ARE pathway inhibitors. We identified MET mutations in 5%, and mutations in four genes of NRF2-ARE pathway (NFE2L2, KEAP1, CUL3 and BACH1) in 10% of 60 pRCC samples. IHC analysis of TMAs of 638 renal cancers showed the correlation of the expression of NQO1 with poor survival outcome (p < .001) and high tumour grade (p < .001) and stage (p < .001) in pRCC. NQO1 mRNA, protein levels and enzymatic activity were increased in 56% of matched pRCC tissue samples and patient-derived cells (PDCs, n = 9). Drug screening revealed that Brusatol and Convallatoxin are potential novel drugs for pRCC. Inhibition of NRF2 represents a novel therapeutic approach for MET-independent pRCC patients.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsNF-E2-Related Factor 2AdultAgedExome SequencingFemaleGene Expression Regulation, NeoplasticHumansKelch-Like ECH-Associated Protein 1MaleMiddle AgedMutationNAD(P)H Dehydrogenase (Quinone)Proto-Oncogene Proteins c-metQuassinsbrusatolKEAP1 protein, humanKelch-Like ECH-Associated Protein 1MET protein, humanNAD(P)H Dehydrogenase (Quinone)NFE2L2 protein, humanNF-E2-Related Factor 2NQO1 protein, humanProto-Oncogene Proteins c-metQuassinsdrug sensitivity profilesNQO1NRF2‐ARE pathwaypapillary renal cell carcinomapatient‐derived cellstranslational medicine

Identifiers

PMID39707614
PMCPMC11789458

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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.