Current Cancer Drug Targets

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

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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.

Abstract:

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

VOLUME: 12
ISSUE: 6
Year: 2012
Page: [693 - 702]
Pages: 10
DOI: 10.2174/156800912801784820