New integrated therapy for glioblastoma considering intratumoral metabolic remodeling with a ketogenic diet

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18391
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kobe University
• Principal Investigator: Tanaka Hirotomo 神戸大学, 医学研究科, 医学研究員 (10569239)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: glioblastoma / Ketogenic diet

Outline of Final Research Achievements

The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev) is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

膠芽腫に対するケトン食療法の効果は一定の見解がないが、多くの報告でカロリー制限した場合の効果は報告されていた。代謝解析の結果、VEGF阻害剤との併用療法によりアスパラギン酸とグルタミン酸がglioma組織において正常脳組織と異なる変化を示した。臨床研究においてVEGF阻害剤とケトン食療法の併用の研究は行われておらず、今後、膠芽腫患者への効果を評価するために併用療法の臨床研究が必要と考えられる。抗血管新生療法とケトン食療法は、単独ではすでに臨床的に用いられており、安全性は確立されているので、併用療法はすぐに導入可能であり、臨床試験を将来的に行っていく必要がある。