EPN-09KETOLYTIC AND GLYCOLYTIC ENZYMATIC EXPRESSION IN PAEDIATRIC EPENDYMOMAS: IMPLICATION FOR KETOGENIC DIET THERAPY

Abstract

EPN-09. KETOLYTIC AND GLYCOLYTIC ENZYMATIC EXPRESSION IN PAEDIATRIC EPENDYMOMAS: IMPLICATION FOR KETOGENIC DIET THERAPY Lisa C.D. Storer1, Angeline Darren1, Simon M.L. Paine2, Jen Kearns3, Robert Layfield4, David A. Walker1, and Richard G. Grundy1; Children’s Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK; Department of Neuropathology, Nottingham University Hospitals NHS Trust, Nottingham, UK; Division of Nutritional Sciences, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Nottingham, UK Ependymoma is the second most common paediatric malignant brain tumour. Overall survival remains relatively poor, and at relapse is dismal. One potential strategy to improve outcome is exploiting the metabolic differences between normal and tumour cells. Under normal physiological conditions, brain cells metabolise glucose for energy. If “starved” of glucose, ketone bodies are metabolised. Mitochondrial defects in brain tumour cells obviate this metabolic flexibility resulting in a dependence on glycolytic energy (Warburg effect). Thus, a high fat, low carbohydrate ketogenic diet (KD) may control tumour growth. We evaluated the expression of ketolytic enzymes; succinyl-CoA:3-oxoacid CoA transferase 1 (OXCT1) and D-b-hydroxybutyrate dehydrogenase 1 (BDH1), both involved in ketone body utilization and the glycolytic enzyme; pyruvate kinase M2 (PKM2), essential for aerobic glycolysis, in 75 paediatric ependymomas by immunohistochemistry. Expression was assessed as low (,20%) or high (.20%).84%showed lowexpression of OXCT1 and 91% of BDH1. Lowexpression of either results in an inability to metabolise ketones. 82% showed high expression of PKM2, increasing the Warburg effect and when combined with low expression of BDH1 (69%) or OXCT1 (83%), the optimal immunohistochemistry profile, arrests ketone metabolism. Children aged ,36 months were 5 times less likely to show high expression of OXCT1 compared to ≥36 months (p 1⁄4 0.0321) and 7 times more likely to show high expression of PKM2 (p 1⁄4 0.0097). The KD therefore offers a potential addition to current therapies including at relapse. However, the KD would need to be carefully evaluated prior to acceptance as a useful additional therapy. Neuro-Oncology 18:iii30–iii39, 2016. doi:10.1093/neuonc/now070.8 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.