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Updated: Aug 21, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma
1University of California San Francisco Comprehensive Cancer Center, CA, USA. brini@medicine.ucsf.edu
Purpose:
To review the biology of renal cell carcinoma (RCC) leading to vascular endothelial growth factor (VEGF) overexpression and the clinical results of VEGF blockade in metastatic RCC.
Methods:
A review of relevant published literature regarding VEGF, von Hippel-Lindau (VHL) gene inactivation and VEGF overexpression in RCC was performed. Further, a review of the mechanism, toxicity, and clinical development of VEGF-targeted therapy in metastatic RCC was undertaken.
Results:
VEGF is the major proangiogenic protein that exerts a biologic effect through interaction with cellular receptors. The majority of sporadic clear-cell RCC tumors are characterized by VHL tumor suppressor gene inactivation. The resulting VHL gene silencing leads to VEGF overexpression. An antibody to VEGF (bevacizumab) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC. Small molecules with inhibitory effects against the VEGF receptor have undergone initial clinical testing in metastatic RCC with substantial objective response rates.
Conclusion:
Therapeutic targeting of VEGF in RCC has strong biologic rationale and preliminary clinical efficacy. Further investigation will determine the optimal timing, sequence, and utility of these agents in RCC.
Insights
Targeting vascular endothelial growth factor (VEGF) in renal cell carcinoma (RCC) shows promise. Inactivation of the von Hippel-Lindau (VHL) gene leads to VEGF overexpression, and blocking VEGF has shown clinical efficacy in metastatic RCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Renal cell carcinoma (RCC) is a complex malignancy.
- Vascular endothelial growth factor (VEGF) plays a critical role in tumor angiogenesis.
- Overexpression of VEGF is a hallmark of clear-cell RCC, often linked to von Hippel-Lindau (VHL) gene inactivation.
Purpose of the Study:
- To elucidate the biological mechanisms driving VEGF overexpression in RCC.
- To review the clinical outcomes of VEGF blockade strategies in metastatic RCC.
Main Methods:
- Literature review of studies on VEGF, VHL gene, and RCC.
- Analysis of the mechanism, toxicity, and clinical development of VEGF-targeted therapies.
Main Results:
- VHL gene inactivation in clear-cell RCC leads to significant VEGF overexpression.
- Bevacizumab, an anti-VEGF antibody, demonstrated prolonged progression-free survival in metastatic RCC patients.
- VEGF receptor inhibitors showed substantial objective response rates in early clinical trials.
Conclusions:
- Targeting VEGF in RCC is biologically rational and shows preliminary clinical effectiveness.
- Further research is needed to optimize the use of VEGF-targeted agents in RCC treatment.
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