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Updated: Jun 10, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Emerging innovative treatment strategies for advanced clear cell renal cell carcinoma
Sharon H Choi1, Yu-Wei Chen1, Justine Panian1
1Division of Hematology Oncology, University of California San Diego, San Diego, CA, United States.
Abstract:
Dramatic advances in biological discoveries, since the 1990s, have continued to reshape the treatment paradigm of metastatic renal cell carcinoma (RCC). Von Hippel Lindau (VHL) gene alterations are associated with pro-angiogenic activity and are central to the pathogenesis of clear cell RCC (ccRCC), the most predominant histologic subtype of RCC. Antiangiogenic strategies revolving around this VHL/HIF/VEGF axis have been shown to improve survival in metastatic ccRCC. The discovery of immune checkpoints and agents that target their inhibition introduced a new treatment paradigm for patients with RCC. While initially approved as monotherapy, studies investigating immune checkpoint inhibitor combinations have led to their approval as the new standard of care, providing durable responses and unprecedented improvements in clinical outcome. Despite these advances, the projected 14 390 deaths in 2024 from RCC underscore the need to continue efforts in expanding and optimizing treatment options for patients with metastatic RCC. This article reviews key findings that have transformed the way we understand and treat metastatic RCC, in addition to highlighting novel treatment strategies that are currently under development.
Insights
Advances in understanding the Von Hippel Lindau (VHL) gene and immune checkpoints have transformed metastatic renal cell carcinoma (RCC) treatment, improving patient survival. Ongoing research aims to further optimize therapies for this deadly cancer.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Metastatic renal cell carcinoma (RCC) treatment has evolved significantly since the 1990s.
- Von Hippel Lindau (VHL) gene alterations drive clear cell RCC (ccRCC) pathogenesis via pro-angiogenic pathways.
- Antiangiogenic therapies targeting the VHL/HIF/VEGF axis have improved survival in metastatic ccRCC.
Purpose of the Study:
- To review key discoveries transforming metastatic RCC understanding and treatment.
- To highlight novel and developing therapeutic strategies for metastatic RCC.
- To underscore the need for continued advancements in RCC treatment.
Main Methods:
- Review of significant biological discoveries and clinical findings in metastatic RCC.
- Analysis of the impact of antiangiogenic and immune checkpoint inhibitor therapies.
- Examination of current and emerging treatment strategies.
Main Results:
- VHL gene alterations are central to ccRCC and targeted by antiangiogenic therapies.
- Immune checkpoint inhibitors, particularly in combination, represent a new standard of care for RCC.
- These advancements have led to durable responses and improved clinical outcomes.
Conclusions:
- The understanding of VHL/HIF/VEGF and immune checkpoints has revolutionized metastatic RCC therapy.
- Despite progress, the high mortality rate necessitates further research and optimization of treatment options.
- Novel therapeutic strategies are under development to address unmet needs in metastatic RCC management.
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