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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
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Targeting G6PD (Glucose-6-Phosphate Dehydrogenase) as a Biomarker of Therapeutic Vulnerability in Renal Cell

Daniel Pinheiro Ferreira1, Ana Carolina Souza Mizael2,3, Julia Victória Bonifácio Cabrieira2,3

  • 1Clinics Hospital, Universidade Federal do Triângulo Mineiro, Uberaba 38025-180, Brazil.

International Journal of Molecular Sciences
|March 28, 2026
PubMed

Insights

Glucose-6-phosphate dehydrogenase (G6PD) is a potential biomarker for kidney cancer aggressiveness. Inhibiting G6PD shows promise as a novel therapeutic strategy for renal cell carcinoma (RCC), particularly in models resistant to current treatments.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Renal cell carcinoma (RCC) incidence is rising globally, with frequent therapeutic resistance to current treatments like VEGF inhibitors.
  • Novel biomarkers and therapeutic targets are crucial for improving outcomes in RCC.
  • Altered glucose-6-phosphate dehydrogenase (G6PD) expression is implicated in various cancers.

Purpose of the Study:

  • To investigate G6PD as a biomarker for RCC aggressiveness and a potential therapeutic target.
  • To evaluate the efficacy of G6PD inhibition in RCC models, including those resistant to VEGF inhibitors.

Main Methods:

  • Analysis of G6PD gene and protein expression in 121 RCC samples using immunohistochemistry.
  • In vitro studies using RCC cell lines (786-O, ACHN) treated with G6PD inhibitor (G6PDi-1) and anti-VEGF agents (cabozantinib, lenvatinib).
  • Assessment of CRISPR and RNAi datasets for G6PD dependency in different RCC subtypes.

Main Results:

  • Higher G6PD mRNA levels in RCC tumors correlated with shorter overall survival in clear cell (ccRCC) and papillary (pRCC) subtypes.
  • Increased G6PD protein expression was observed in pRCC and associated with pathological features.
  • G6PD dependency was higher in ccRCC, and high G6PD expression was noted in lenvatinib-resistant cell lines.
  • G6PDi-1 impaired viability, migration, and clonogenic capacity in 786-O cells, while cabozantinib showed stronger effects in ACHN cells.

Conclusions:

  • G6PD serves as a potential biomarker for RCC tumor aggressiveness.
  • G6PDi-1 demonstrates potential as a therapeutic agent in RCC models, especially for treatment-resistant cases.
Keywords:
G6PDrenal cell carcinomatherapeutic targettumor aggressiveness

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