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- W2495737701 abstract "Background: Sunitinib is a multi-targeted agent approved for treatment of a number of cancers. However, since approval, data has continually emerged relating to toxicity profiles including hypertension, hand-foot syndrome and fatigue. Underlying mechanisms are unresolved. It has been hypothesised that the multi-parameter toxicity profile is related to ‘on-target’ kinase inhibition in ‘off-target’ tissues. Methods: To interrogate off-target effects, the Zeptosens Reverse Phase protein Array (RPA) platform was used to assess tissues obtained from mice treated with sunitinib (40 mg/kg) for 4 weeks. Additional tissue was collected for histological analyses and pathophysiologic changes assessed. Results: RPA data analyses on all organs collected (heart, kidney, liver, brain, intestine and skin) revealed the presence of differentially expressed proteins associated with damage and/or stress. Of note, Cyclin D1, MEK and phosphorylated-p21(CIP/WAF1) expression increased by 1.8-fold (p Conclusions: Implementation of a combined histopathologic/ RPA approach may provide a sensitive method to mechanistically elucidate the off-target toxicity sequelae associated with TKIs approved in the oncology setting. Work was supported by an EU funded Industry Academia Pathways and Partnerships Marie Curie Award (AngioTox) Grant Number 251528. RPAs were performed at Bayer Technology Services, Leverkusen, Germany. Citation Format: Alice C. O’Farrell, Adam Lafferty, Ian Miller, Rhys Evans, Maurice Cary, David Murray, Marina Alamanou, Girish Mallya Udupi, Liam Shiels, William M. Gallagher, Annette T. Byrne. Proteomic analysis of off-target toxicities following treatment with the tyrosine kinase inhibitor sunitinib. [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 3010." @default.
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- W2495737701 date "2016-07-15" @default.
- W2495737701 modified "2023-09-27" @default.
- W2495737701 title "Abstract 3010: Proteomic analysis of off-target toxicities following treatment with the tyrosine kinase inhibitor sunitinib" @default.
- W2495737701 doi "https://doi.org/10.1158/1538-7445.am2016-3010" @default.
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