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Autophagy inhibition is the next step in the treatment of glioblastoma patients following the Stupp era

Abstract

It has now been nearly 15 years since the last major advance in the treatment of patients with glioma. “The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity”. Autophagy is primarily a survival pathway, literally self-eating, that is utilized in response to stress (such as radiation and chemotherapy), enabling clearance of effete protein aggregates and multimolecular assemblies. Promising results have been observed in patients with glioma for over a decade now when autophagy inhibition with chloroquine derivatives coupled with conventional therapy. The application of autophagy inhibitors, the role of immune cell-induced autophagy, and the potential role of novel cellular and gene therapies, should now be considered for development as part of this well-established regimen.

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Acknowledgements

This work was supported in part by funding received from NCI R01 CA181450-on “Pancreatic Ductal Adenocarcinoma is a disease of constitutive autophagy” and a subcontract on DARPA-BAA-14-14; DARPA Big Mechanism Proposal. AIMCancer: Automated Integration of Mechanisms in Cancer.

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Zhang, X., Deibert, C.P., Kim, WJ. et al. Autophagy inhibition is the next step in the treatment of glioblastoma patients following the Stupp era. Cancer Gene Ther 28, 971–983 (2021). https://doi.org/10.1038/s41417-020-0205-8

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