Abstract 630: Interleukin-8 as a potential mediator for renal cell carcinoma resistance to antiangiogenic sunitinib therapy

Abstract

Abstract 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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 630.