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Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma

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Abstract

Autophagy is an evolutionarily conserved catabolic process that plays an essential role in maintaining cellular homeostasis by degrading unneeded cell components. When exposed to hostile environments, such as hypoxia or nutrient starvation, cells hyperactivate autophagy in an effort to maintain their longevity. In densely packed solid tumors, such as glioblastoma, autophagy has been found to run rampant due to a lack of oxygen and nutrients. In recent years, targeting autophagy as a way to strengthen current glioblastoma treatment has shown promising results. However, that protective autophagy inhibition or autophagy overactivation is more beneficial, is still being debated. Protective autophagy inhibition would lower a cell’s previously activated defense mechanism, thereby increasing its sensitivity to treatment. Autophagy overactivation would cause cell death through lysosomal overactivation, thus introducing another cell death pathway in addition to apoptosis. Both methods have been proven effective in the treatment of solid tumors. This systematic review article highlights scenarios where both autophagy inhibition and activation have proven effective in combating chemoresistance and radioresistance in glioblastoma, and how autophagy may be best utilized for glioblastoma therapy in clinical settings.

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Acknowledgements

The work was supported in part by an award from the Soy Health Research Program (SHRP, United Soybean Board, Chesterfield, MO, USA), an investigator initiated research grant (SCIRF-2015-I-01) from South Carolina Spinal Cord Injury Research Fund (Columbia, SC, USA), and earlier R01 grants (CA-091460, and NS-057811) from the National Institutes of Health (Bethesda, MD, USA).

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Authors and Affiliations

  1. Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Building 2, Room C11, 6439 Garners Ferry Road, Columbia, SC, 29209, USA

    Matthew A. Taylor & Swapan K. Ray

  2. Departments of Medicine and Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Bhaskar C. Das

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  1. Matthew A. Taylor
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Correspondence to Swapan K. Ray.

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Taylor, M.A., Das, B.C. & Ray, S.K. Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma. Apoptosis 23, 563–575 (2018). https://doi.org/10.1007/s10495-018-1480-9

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