Complete targeting of glioma stem cells through an original, multi-layered approach

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02908
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Yamagata University
• Principal Investigator: Chifumi KITANAKA 山形大学, 医学部, 教授 (70260320)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膠芽腫

Outline of Final Research Achievements

In this project, we focused on the mitochondrial respiratory chain as a possible vulnerability specific to glioma stem cells. The results revealed that the expression levels of the components of the respiratory chain encoded by the mitochondrial DNA were increased in glioma stem cells compared to their differentiated counterparts and that glioma stem cells were dependent on the respiratory chain for their survival. We then screened a panel of approved drugs known to inhibit the function of the respiratory chain, and successfully identified verteporfin, a therapeutic agent for age-related macular degeneration, as a glioma stem cell-specific drug that can induce extensive cell death in glioma stem cells while sparing their differentiated counterparts or normal cells.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

がん（悪性新生物）は長年にわたり我が国の死亡原因圧倒的第１位を維持しており、がんの克服は国家的にも重要な課題である。本課題はがんの再発・転移の主要因と考えられているがん幹細胞に着目し、そのがん幹細胞に作用することで再発・転移を防ぎがん根治が期待できるがん幹細胞治療薬開発を目指そうとする課題である。本課題では特に悪性脳腫瘍のがん幹細胞が持つ「アキレス腱」に着目し、そこを攻撃する薬剤を見出した点がユニークなものとなっている。本課題で得られた成果は難治を極める悪性脳腫瘍の長期治療成績の改善に大きく貢献することが期待される。