Interleukin-8 Mediates Resistance to Antiangiogenic Agent Sunitinib in Renal Cell Carcinoma
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- Dan Huang
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Yan Ding
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Ming Zhou
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Brian I. Rini
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- David Petillo
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Chao-Nan Qian
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Richard Kahnoski
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- P. Andrew Futreal
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Kyle A. Furge
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
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- Bin Tean Teh
- Authors' Affiliations: 1Laboratory of Cancer Genetics, 2Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan; Departments of 3Anatomic Pathology and 4Solid Tumor Oncology and Urology, Cleveland Clinic, Cleveland, Ohio; 5The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 6Department of Urology, Spectrum Health, Grand Rapids, Michigan; and 7Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
説明
<jats:title>Abstract</jats:title> <jats:p>The broad spectrum kinase inhibitor sunitinib is a first-line therapy for advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Unfortunately, most patients develop sunitinib resistance and progressive disease after about 1 year of treatment. In this study, we evaluated the mechanisms of resistance to sunitinib to identify the potential tactics to overcome it. Xenograft models were generated that mimicked clinical resistance to sunitinib. Higher microvessel density was found in sunitinib-resistant tumors, indicating that an escape from antiangiogenesis occurred. Notably, escape coincided with increased secretion of interleukin-8 (IL-8) from tumors into the plasma, and coadministration of an IL-8 neutralizing antibody resensitized tumors to sunitinib treatment. In patients who were refractory to sunitinib treatment, IL-8 expression was elevated in ccRCC tumors, supporting the concept that IL-8 levels might predict clinical response to sunitinib. Our results reveal IL-8 as an important contributor to sunitinib resistance in ccRCC and a candidate therapeutic target to reverse acquired or intrinsic resistance to sunitinib in this malignancy. Cancer Res; 70(3); 1063–71</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 70 (3), 1063-1071, 2010-01-31
American Association for Cancer Research (AACR)
