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• W2499408218 abstract "Background: Androgen receptor (AR) expression has been reported in renal cell carcinoma but its biological role remains elusive. Sunitinib is a potent anti-angiogenic drug approved for the treatment of advanced renal cell carcinoma (RCC). However, eventually RCC tumors develop drug resistance. We have hypothesized that tumor cells resistance to sunitinib is associated with kinome reprograming and anti-apoptotic genes upregulation. To date, there is no report on the association between AR expression and resistance to TKI such as sunitinib in RCC. Our study was designed to investigate the role of AR in sunitinib resistance in RCC. We used our previously reported sunitinib resistant ccRCC cells and patient derived xenograft models. Methods: Human RCC cell lines; 786-0, 786-0R (sunitinib resistant), C2, C2R (sunitinib resistant), ACHN and Caki 2 were utilized to determine sensitivity or resistance to sunitinib. Patient derived xenograft (PDX) models of advance and metastatic RCC and RCC cell lines, sensitive and resistant tumors were used to detect AR expression by qRT-PCR, immunohistochemistry and Western blot analysis. Reverse phase protein array (RPPA) was used to assess 249 protein including AR in sunitinib sensitive and resistant tumors. Results: Our qRT-PCR data showed an increase by 1000 folds in mRNA levels of AR in our sunitinib resistant cell lines. Similarly, RPPA data revealed AR to be increased in sunitinib resistant RCC PDX tumors. This observation was confirmed by Western blot analysis. Conclusion: Overall our data suggest the potential role of AR and its association with resistance to sunitinib. Ongoing studies are testing the in vitro and in vivo combination treatment of RCC models with sunitinib and AR antagonists. Citation Format: Remi M. Adelaiye-Ogala, Sreenivasulu Chintala, Ashley Orillion, Piergiorgio Pettazzoni, May Elbanna, Bennett Elzey, Kiersten Marie Miles, Chinghai Kao, Giulio F. Draetta, Roberto Pili. Androgen receptor expression is associated with sunitinib resistance in renal cell carcinoma models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2126." @default.
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• W2499408218 date "2016-07-15" @default.
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• W2499408218 title "Abstract 2126: Androgen receptor expression is associated with sunitinib resistance in renal cell carcinoma models" @default.
• W2499408218 doi "https://doi.org/10.1158/1538-7445.am2016-2126" @default.
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