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- W2334211189 abstract "Introduction: GIST, the most common mesenchymal malignancies of the GI tract, are characterized by gain-of-function mutations in KIT and PDGFRα receptors. Imatinib and sunitinib are tyrosine kinase inhibitors (TKI) currently approved for the treatment of GIST. Recent evidence suggests that GIST cells acquire secondary resistance to TKI through activation of alternative signaling pathways. We hypothesize that gene therapy with replicative vector oncolysis (virotherapy) can be utilized to improve efficacy of TKI and overcome GIST resistance to treatment. Objectives: To determine if a panel of oncolytic adenoviruses in combination with imatinib and sunitinib, results in synergistic inhibition of GIST cell proliferation. Results: GIST882 and GIST-T1 cells were subjected to imatinib and sunitinib treatment in combination with a panel of oncolytic adenoviruses (Ad5, Ad5RGD, Ad5pK7, and Ad5 - Ad3 fiber knob), to assess their inhibitory effects on cell proliferation. The Ad5/3 vector had the best rate of gene transfer and cytolytic effect. The greatest anti-proliferative effects were observed with 100 viral particles/cell of the Ad5/3 vector combined with TKI concentrations of 0.1 µM in GIST-T1 cell line. The combination of TKI and oncolytic adenoviruses showed greater inhibition of GIST cell proliferation (78% decrease) when compared to TKI alone (58% decrease) and viral therapy alone (23% decrease, p Conclusions: The oncolytic adenovirus Ad5/3 infects and inhibits GIST cell proliferation both in vitro and ex vivo. Virotherapy with Ad5/3 has synergistic anti-proliferative effects with TKI and may help overcome GIST resistance to KIT targeted therapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1171." @default.
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- W2334211189 date "2010-04-15" @default.
- W2334211189 modified "2023-09-27" @default.
- W2334211189 title "Abstract 1171: Gastrointestinal stromal tumors (GIST) cell proliferation inhibition with combined adenoviral and molecular targeted therapy" @default.
- W2334211189 doi "https://doi.org/10.1158/1538-7445.am10-1171" @default.
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