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Abstract #1717

DCE/DSC MRI Studies of Intracranial Mouse Glioma: Enhanced Anti-Vascular/anti-Tumor Efficacy of Cediranib Via Combination with the Autophagy Inhibitor Quinacrine

Merryl R. Lobo1, 2, Sarah Green3, Matthias C. Schabel2, Yancey Gillespie4, Randall Woltjer3, Martin Pike, 12

1Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, United States; 2Advanced Imaging Research Center, Oregon Health and Science University, Portland, OR, United States; 3Department of Pathology, Oregon Health and Science University, Portland, OR, United States; 4Departments of Surgery, Microbiology and Cell, Developmental & Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, United States

Despite extensive malignant glioma vascularity, anti-angiogenic therapy largely fails to induce durable responses. Autophagy, a cellular degradation pathway, can promote survival and drug resistance in tumor cells, and its late-stage inhibition can induce cell death. Using a novel treatment combination with the intracranial 4C8 mouse glioma model, we documented a synergistic increase in anti-vascular/anti-tumor efficacy of anti-angiogenic inhibitor Cediranib in combination with the autophagy inhibitor Quinacrine, using a comprehensive DCE/DSC perfusion MRI approach and immunohistology. We a showed markedly decreased tumor perfusion, tumor growth, increased tumor necrosis and improved survival, suggesting a new and promising treatment avenue for malignant glioma.

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