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- W2006809310 abstract "INTRODUCTION: Acquired resistance threatens the potential of anti-angiogenic therapy. Xenograft models of acquired anti-angiogenic therapy resistance are lacking and often fail to reflect changes human tumors acquire during prolonged serial treatment with anti-angiogenic therapy because of the significantly shorter lifespan of tumor-bearing mice. To create a xenograft model of bevacizumab-resistant GBM allowing temporal definition of changes during resistance to VEGF blockade, we created a model whereby serially passaged xenografts were continually exposed to bevacizumab versus IgG control antibody over 5 generations in vivo. METHODS: We treated 5 subcutaneous U87 glioma cell line-derived xenografts with bevacizumab or IgG, explanted the least responsive xenograft and reimplanted it subcutaneously, then repeated this pattern of treatment followed by explantation and reimplantation of the least responsive xenograft for 4 more generations, generating 5 generations of U87-IgG and U87-BevR xenografts. Western blot assessed temporal changes. RESULTS: Subcutaneous fifth generation U87-BevR were unresponsive to bevacizumab versus IgG (P=0.8). Bevacizumab caused U87-IgG to regress (P CONCLUSIONS: Our novel model of acquired anti-angiogenic therapy resistance showed that acquired resistance increases parenchymal and perivascular invasion with some changes (increased c-Met, VEGFR2, and phosphorylated STAT3) occurring early and lasting throughout resistance, while other changes like alpha5beta1 integrin upregulation peaked later and decreased over time. The ability of this model to replicate prolonged anti-angiogenic therapy duration seen in patients should generate a molecular profile of anti-angiogenic therapy resistance, and should define which resistance-associated changes are driver versus passenger alterations. Citation Format: Arman Jahangiri, Michael De Lay, W. Shawn Carbonell, Liane Miller, Manish K. Aghi. Serial treatment-transplant xenograft model of Bevacizumab-resistance reveals temporal induction of markers associated with disease progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1610. doi:10.1158/1538-7445.AM2013-1610" @default.
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- W2006809310 date "2013-04-15" @default.
- W2006809310 modified "2023-09-25" @default.
- W2006809310 title "Abstract 1610: Serial treatment-transplant xenograft model of Bevacizumab-resistance reveals temporal induction of markers associated with disease progression." @default.
- W2006809310 doi "https://doi.org/10.1158/1538-7445.am2013-1610" @default.
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