Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors

Juliette Servante _, Jasper Estranero, Lisethe Meijer, Rob Layfield and Richard Grundy

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Oncotarget. 2018; 9:35266-35277. https://doi.org/10.18632/oncotarget.26186

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Juliette Servante1, Jasper Estranero2, Lisethe Meijer2, Rob Layfield1 and Richard Grundy2

1School of Life Sciences, University of Nottingham, Medical School, Nottingham, NG7 2UH, UK

2Children’s Brain Tumor Research Centre, Medical School, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

Correspondence to:

Juliette Servante, email: [email protected]

Keywords: autophagosome; autophagy; childhood brain tumors; chloroquine; mTOR

Received: January 20, 2018     Accepted: August 27, 2018     Published: October 16, 2018


Brain tumors are the leading cause of cancer-related death in children and are the most challenging childhood cancer in relation to diagnosis, treatment, and outcome. One potential novel strategy to improve outcomes in cancer involves the manipulation of autophagy, a fundamental process in all cells. In cancer, autophagy can be thought of as having a “Janus”-like duality. On one face, especially in the early phases of cancer formation, autophagy can act as a cellular housekeeper to eliminate damaged organelles and recycle macromolecules, thus acting as tumor suppressor. On the other face, at later stages of tumor progression, autophagy can function as a pro-survival pathway in response to metabolic stresses such as nutrient depravation, hypoxia and indeed to chemotherapy itself, and can support cell growth by supplying much needed energy. In the context of chemotherapy, autophagy may, in some cases, mediate resistance to treatment. We present an overview of the relevance of autophagy in central nervous system tumors including how its chemical modulation can serve as a useful adjunct to chemotherapy, and use this knowledge to consider how targeting of autophagy may be relevant in pediatric brain tumors.

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