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Updated: Aug 10, 2025
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Clear Cell Renal Cell Carcinoma: From Biology to Treatment
Adam M Kase1, Daniel J George2, Sundhar Ramalingam2
1Mayo Clinic, Division of Hematology Oncology, Jacksonville, FL 32224, USA.
Abstract:
The majority of kidney cancers are detected incidentally and typically diagnosed at a localized stage, however, the development of regional or distant disease occurs in one-third of patients. Over 90% of kidney tumors are renal cell carcinomas, of which, clear cell is the most predominate histologic subtype. Von Hippel Lindau (VHL) gene alterations result in the overexpression of growth factors that are central to the pathogenesis of clear cell carcinoma. The therapeutic strategies have revolved around this tumor suppressor gene and have led to the approval of tyrosine kinase inhibitors (TKI) targeting the vascular endothelial growth factor (VEGF) axis. The treatment paradigm shifted with the introduction of immune checkpoint inhibitors (ICI) and programed death-1 (PD-1) inhibition, leading to durable response rates and improved survival. Combinations of TKI and/or ICIs have become the standard of care for advanced clear cell renal cell carcinoma (ccRCC), changing the outlook for patients, with several new and promising therapeutic targets under development.
Insights
Clear cell renal cell carcinoma (ccRCC) treatments have advanced significantly. Combining targeted therapies like tyrosine kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICIs) improves patient survival for advanced kidney cancer.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Most kidney cancers are diagnosed early, but one-third develop advanced disease.
- Clear cell renal cell carcinoma (ccRCC) is the predominant subtype, linked to Von Hippel Lindau (VHL) gene alterations.
- VHL gene mutations drive growth factor overexpression, crucial in ccRCC development.
Purpose of the Study:
- To review the evolution of therapeutic strategies for clear cell renal cell carcinoma.
- To highlight the impact of targeted therapies and immunotherapies on ccRCC treatment.
- To discuss current standards of care and emerging targets for advanced ccRCC.
Main Methods:
- Literature review of therapeutic strategies for ccRCC.
- Analysis of the role of Von Hippel Lindau (VHL) gene in ccRCC pathogenesis.
- Evaluation of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in ccRCC treatment.
Main Results:
- Tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis were developed based on VHL pathway understanding.
- Immune checkpoint inhibitors (ICIs), including programed death-1 (PD-1) inhibitors, have shown durable responses and improved survival.
- Combination therapies of TKIs and/or ICIs are now standard for advanced ccRCC.
Conclusions:
- Therapeutic strategies for ccRCC have shifted towards targeted therapies and immunotherapies.
- Combination treatments offer improved outcomes for patients with advanced clear cell renal cell carcinoma.
- Ongoing research is exploring novel therapeutic targets for ccRCC.
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