Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106


High CXCR4 Expression Correlates with Sunitinib Poor Response in Metastatic Renal Cancer

Author(s): C. D'Alterio, L. Portella, A. Ottaiano, M. Rizzo, G. Carteni, S. Pignata, G. Facchini, S. Perdona, G. Di Lorenzo, R. Autorino, R. Franco, A. La Mura, O. Nappi, G. Castello, S. Scala.


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

Keywords: CXCR4, first-line therapy, mRCC, response to therapy, sunitinib, survival analyses, Response Evaluation Criteria in Solid Tumors (RECIST), ANOVA, GAPDH expression, CXCR4-Fuhrman grading concomitant evaluation

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Article Details

Year: 2012
Page: [693 - 702]
Pages: 10
DOI: 10.2174/156800912801784820