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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