Presentation Abstract

Abstract Number: 630
Presentation Title: Interleukin-8 as a potential mediator for renal cell carcinoma resistance to antiangiogenic sunitinib therapy
Presentation Time: Sunday, Apr 18, 2010, 2:00 PM - 5:00 PM
Location: Exhibit Hall A-C, Poster Section 23
Poster Section: 23
Poster Board Number: 27
Author Block: Dan Huang1, Yan Ding1, Ming Zhou2, Brian Rini2, David Petillo1, Chao-Nan Qian1, Richard Kahnoski3, P. Andrew Futreal4, Kyle A. Furge1, Bin Tean Teh1. 1Van Andel Research Inst., Grand Rapids, MI; 2Cleveland Clinic, Cleveland, OH; 3Spectrum Health, Grand Rapids, MI; 4Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Abstract Body: Sunitinib is considered the first line therapy for advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Unfortunately, most patients exhibit progressive disease after about one year of treatment. The mechanisms of progression are poorly understood. The aim of this study was to evaluate the mechanism of resistance to sunitinib and to identify potential targets to overcome sunitinib resistance. We generated xenograft models that mimicked clinical resistance to sunitinib. Higher microvessel density was found in sunitinib-resistant tumors, which indicated that an escape from anti-angiogenesis occurred in these tumors. This escape coincided with increased tumor secretion of interleukin-8 (IL-8) into the plasma. Co-administration of an IL-8 neutralizing antibody resensitized these tumors to sunitinib treatment, demonstrating the functional contribution of IL-8 to sunitinib resistance. Immunohistochemical staining showed that IL-8 expression was elevated in ccRCC tumors from patients who were refractory to sunitinib treatment, indicating IL-8 levels may predict clinical response to sunitinib. In conclusion, our results demonstrate that IL-8 is an important contributor, among others, to sunitinib resistance in ccRCC. IL-8 may serve as a therapeutic target for treatment of sunitinib resistant ccRCC, as well as a biomarker for both acquired and intrinsic sunitinib resistance.