Identification and analysis of drugs for overcoming hypoxia in glioblastoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15602
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Keio University
• Principal Investigator: Koike Naoyoshi 慶應義塾大学, 医学部(信濃町), 助教 (60464913)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 低酸素 / 放射線治療 / 膠芽腫 / 2－ニトロイミダゾール化合物 / theranostics

Outline of Final Research Achievements

The radioresistance of glioblastoma is caused by the hypoxic region in the tumor. The nitroimidazole compounds that accumulates specifically in the hypoxic region were analyzed for overcoming radioresistance. Among nitroimidazole compounds, doranidazole had a radiosensitizing effect in the hypoxic region of glioblastoma and a cell-killing effect by itself. The mechanism of cell death by doranidazole was mitochorial stress. In the allogeneic orthotopic mouse brain tumor model, the combined use of doranidazole and irradiation contributed to prolongation of mouse survival.

Free Research Field

放射線腫瘍学

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は放射線治療抵抗性であることが多く、膠芽腫を制御するために放射線増感剤が求められている。本研究で膠芽腫に対する有望な放射線増感剤としてドラニダゾールを見出した。低酸素マーカーとして診療で使用されている18F-FMISOと同じ2-ニトロイミダゾール化合物であり、薬剤集積と効果予測とがたてやすいという利点がある。臨床試験に進む前段階の研究を行うことができた。