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Updated: May 23, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
High CXCR4 expression correlates with sunitinib poor response in metastatic renal cancer
C D' Alterio1, L Portella, A Ottaiano
1Department of Oncological Immunology, Istituto per lo Studio e la Cura dei Tumori "Pascale", Naples, Italy.
Background:
Almost 30% of the sunitinib-treated patients for metastatic renal carcinoma (mRCC) do not receive a clinical benefit. Convincing evidences demonstrated a cross talk between the VEGF and CXCR4 pathways. It was hypothesized that CXCR4 expression in primary renal cancer could predict sunitinib responsiveness.
Patients And Methods:
In this exploratory study sixty-two mRCC patients receiving sunitinib as first-line treatment were evaluated for CXCR4 expression through immunohistochemistry (IHC). Correlations between CXCR4 expression, baseline patients and tumour characteristics were studied by contingency tables and the chi-square test. Univariable analysis was performed with the log-rank test, and the Cox model was applied for multivariable analysis.
Results:
The objective response rate of sunitinib first-line therapy was 35.5% (22/62) with a disease control rate (response and stable disease) of 62.9% (39/62). CXCR4 expression was absent/low in 30 (48.4%), moderate in 17 (27.4%), and high in 15 (24.2%) tumors respectively. Low or absent CXCR4 expression predicted response to sunitinib therapy. Moreover, Fuhrman grading and concomitant, CXCR4 and Fuhrman grading, strongly predicted sunitinib first line therapy responsiveness on progression-free survival and overall survival.
Conclusions:
High CXCR4 expression correlates with sunitinib poor response in metastatic renal cancer.
Insights
High CXCR4 expression indicates poor response to sunitinib in metastatic renal cancer patients. Low or absent CXCR4 predicts better outcomes, guiding treatment decisions for renal cell carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Sunitinib is a tyrosine kinase inhibitor used for metastatic renal carcinoma (mRCC).
- Approximately 30% of mRCC patients do not benefit from sunitinib treatment.
- Cross-talk between VEGF and CXCR4 pathways suggests a role for CXCR4 in sunitinib resistance.
Purpose of the Study:
- To investigate if CXCR4 expression in primary renal cancer can predict response to sunitinib therapy.
- To evaluate the correlation between CXCR4 expression and patient/tumor characteristics.
- To determine the prognostic value of CXCR4 expression for progression-free and overall survival.
Main Methods:
- An exploratory study involving 62 mRCC patients receiving first-line sunitinib.
- CXCR4 expression assessed using immunohistochemistry (IHC).
- Statistical analyses included chi-square test, log-rank test, and Cox regression model.
Main Results:
- Objective response rate was 35.5%; disease control rate was 62.9%.
- CXCR4 expression was absent/low in 48.4%, moderate in 27.4%, and high in 24.2% of tumors.
- Low/absent CXCR4 expression predicted sunitinib response.
- Combined CXCR4 and Fuhrman grading predicted survival outcomes.
Conclusions:
- High CXCR4 expression is associated with poor response to sunitinib in mRCC.
- CXCR4 expression serves as a potential predictive biomarker for sunitinib therapy in renal cell carcinoma.
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