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Updated: Aug 11, 2026
The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Understanding the importance of smart drugs in renal cell carcinoma
Jean-Jacques Patard1, Nathalie Rioux-Leclercq, Patricia Fergelot
1Department of Urology, Rennes University Hospital, France. jean-jacques.patard@chu-rennes.fr
Objective:
To understand the mode of action of the currently most investigated new drugs in renal cell carcinoma (RCC) and ultimately to analyze what should be the role of the urologist in this new therapeutic era.
Methods:
A comprehensive review of the peer-reviewed literature was performed on the topic of molecular pathways involved in RCC angiogenesis, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) and targeted molecular therapy for RCC.
Results:
Von Hippel-Lindau (VHL) disease has provided a model for understanding that the early inactivation of the VHL gene was responsible for accumulation of hypoxia-inducible factor and therefore activation of hypoxia-inducible genes such as VEGF, platelet-derived growth factor, erythropoietin, carbonic anhydrase IX and tumor growth factor alpha. The fact that such VHL inactivation also was found in up to 70% of sporadic RCC has been the rationale for developing new drugs targeting VEGF, VEGFR, platelet-derived growth factor receptor and tyrosine kinase receptors that are required for intracellular transduction.
Conclusion:
Initial results from phase 2 trials in metastatic disease are very promising. There is a strong rationale for initiating adjuvant trials with those kind of agents in patients with high-risk localised tumors. Urologists who have a good understanding of prognostic parameters in localised RCC particularly should be involved in such new approaches.
Insights
New targeted therapies for renal cell carcinoma (RCC) focus on inhibiting vascular endothelial growth factor (VEGF) and its receptors. Urologists play a key role in managing localized RCC and integrating these novel treatments.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Renal cell carcinoma (RCC) pathogenesis involves VHL gene inactivation, leading to hypoxia-inducible factor accumulation and activation of genes like VEGF.
- This mechanism is implicated in up to 70% of sporadic RCC cases, providing a rationale for targeted therapies.
Purpose of the Study:
- To elucidate the mechanism of action for novel RCC drugs.
- To define the urologist's role in the evolving therapeutic landscape of RCC.
Main Methods:
- Comprehensive literature review on RCC molecular pathways, angiogenesis, VEGF, VEGFR, and targeted molecular therapy.
- Analysis of peer-reviewed studies on targeted agents.
Main Results:
- New drugs targeting VEGF, VEGFR, and tyrosine kinases show promising early results in phase 2 trials for metastatic RCC.
- VHL gene inactivation is a key driver in RCC, explaining the efficacy of anti-VEGF/VEGFR therapies.
Conclusions:
- Targeted therapies demonstrate significant promise in metastatic RCC.
- Adjuvant trials with these agents are warranted for high-risk localized RCC.
- Urologists' expertise in localized RCC prognosis is crucial for implementing these new treatment strategies.
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