MP72-06 CORRELATION OF THE INSULIN RECEPTOR EXPRESSION AND THE RESISTANCE TO VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITORS IN ADVANCED CLEAR CELL RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II1 Apr 2018MP72-06 CORRELATION OF THE INSULIN RECEPTOR EXPRESSION AND THE RESISTANCE TO VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITORS IN ADVANCED CLEAR CELL RENAL CELL CARCINOMA Masayuki Takahashi, Kei Daizumoto, Yayoi Fukuhara, Keisuke Ozaki, Megumi Tsuda, Yoshito Kusuhara, Hidehisa Mori, Tomoya Fukawa, Yasuyo Yamamoto, Kunihisa Yamaguchi, Tomoharu Fukumori, and Hiroomi Kanayama Masayuki TakahashiMasayuki Takahashi More articles by this author , Kei DaizumotoKei Daizumoto More articles by this author , Yayoi FukuharaYayoi Fukuhara More articles by this author , Keisuke OzakiKeisuke Ozaki More articles by this author , Megumi TsudaMegumi Tsuda More articles by this author , Yoshito KusuharaYoshito Kusuhara More articles by this author , Hidehisa MoriHidehisa Mori More articles by this author , Tomoya FukawaTomoya Fukawa More articles by this author , Yasuyo YamamotoYasuyo Yamamoto More articles by this author , Kunihisa YamaguchiKunihisa Yamaguchi More articles by this author , Tomoharu FukumoriTomoharu Fukumori More articles by this author , and Hiroomi KanayamaHiroomi Kanayama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2290AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) demonstrate the significant efficacy for advanced clear cell renal cell carcinoma (ccRCC), however, it eventually becomes resistant to VEGFR-TKIs during the treatment. So far, the mechanisms for the resistance to VEGFR-TKIs remain to be fully elucidated. Previously we have identified the gene set which could predict poor prognosis of ccRCC patients (Takahashi M et.al., Proc Natl Acad Sci U S A., 98: 9754, 2001). We examined whether the insulin receptor (INSR) expression in the gene set may correlate with the resistance to VEGFR-TKIs. METHODS The INSR expression was examined immunohistochemically in the nephrectomy specimens of the RCC patients (n=33) who then received axitinib as the VEGFR-TKI and correlated with their survival outcome. We compared the INSR expression of the nephrectomy or metastasectomy specimens before and after the administration of VEGFR-TKIs in 5 cases. The INSR expression of the human renal glomerular endothelial cells (HGEC) was compared before and after the administration of axitinib by Western blotting. In addition, we established patient derived Xenograft model (PDX) of ccRCC. Tumors of PDX were resected when it regrew and showed the resistance for axitinib and the INSR expression was compared before and after the treatment by Western blotting. RESULTS The INSR was expressed at the vessels surrounding tumor cells. Progression-free survival (PFS) was significantly shorter in the INSR-negative group than in the INSR-positive group. Multivariate analysis revealed that the INSR expression was the significantly independent predictor of PFS. In the specimens resected after VEGFR-TKI, the INSR expression was more frequently decreased. As the concentration of axitinib increased, the INSR expression in the HGEC was decreased. The tumors of PDX that were resected after demonstrating the resistance to axitinib had the decreased INSR expression. CONCLUSIONS The decreased INSR expression could be correlated with the resistance to VEGFR-TKI and its expression may be useful in selecting appropriate drugs for advanced ccRCC patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e954 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Masayuki Takahashi More articles by this author Kei Daizumoto More articles by this author Yayoi Fukuhara More articles by this author Keisuke Ozaki More articles by this author Megumi Tsuda More articles by this author Yoshito Kusuhara More articles by this author Hidehisa Mori More articles by this author Tomoya Fukawa More articles by this author Yasuyo Yamamoto More articles by this author Kunihisa Yamaguchi More articles by this author Tomoharu Fukumori More articles by this author Hiroomi Kanayama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...