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Updated: Jun 4, 2025

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

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Exploiting NRF2-ARE pathway activation in papillary renal cell carcinoma

Silvia Angori1, Harini Lakshminarayanan1, Amir Banaei-Esfahani1

  • 1Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

International Journal of Cancer
|December 21, 2024
PubMed

Insights

Papillary renal cell carcinoma (pRCC) lacks targeted treatments. This study reveals NRF2-ARE pathway involvement in pRCC, identifying NQO1 as a poor survival marker and potential drug targets like Brusatol for MET-independent pRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Papillary renal cell carcinoma (pRCC) is the second most common kidney cancer subtype.
  • Currently, pRCC lacks specific targeted therapies, especially for non-MET-driven cases.
  • The NRF2-ARE pathway is implicated in pRCC development and progression.

Purpose of the Study:

  • To investigate the role of the NRF2-ARE pathway in pRCC.
  • To identify potential therapeutic targets for pRCC, particularly MET-independent subtypes.

Main Methods:

  • Copy number analysis and Whole Exome Sequencing of 60 pRCC samples.
  • Immunohistochemistry (IHC) for NQO1 expression on tissue microarrays (TMAs).
  • Enzymatic activity assays and drug profiling of patient-derived pRCC cells (PDCs) with NRF2-ARE pathway inhibitors.

Main Results:

  • Mutations in MET (5%) and NRF2-ARE pathway genes (10%) were identified in pRCC samples.
  • Increased NQO1 expression correlated with poor survival, high tumor grade, and advanced stage in pRCC.
  • NQO1 levels and activity were elevated in 56% of pRCC tissues and PDCs, with Brusatol and Convallatoxin showing promise as novel therapeutic agents.

Conclusions:

  • The NRF2-ARE pathway is significantly involved in pRCC pathogenesis.
  • NQO1 serves as a prognostic biomarker for poor survival in pRCC.
  • Inhibiting the NRF2 pathway presents a novel therapeutic strategy for MET-independent pRCC.
Keywords:
NQO1NRF2‐ARE pathwaydrug sensitivity profilespapillary renal cell carcinomapatient‐derived cellstranslational medicine

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