A research project aimed at developing glioma stem cell-targeting therapies through a unique and multi-faceted strategy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03040
• 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: Kitanaka Chifumi 山形大学, 医学部, 教授 (70260320)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膠芽腫

Outline of Final Research Achievements

In this project, drawing on the findings from our previous projects, we focused on 1) the development of drugs that specifically kills glioma stem cells (GSCs) as well as the identification of molecules differentially expressed between GSCs and non-GSCs, 2) the search for methods to therapeutically target the pathway leading to JNK activation required for stemness maintenance, 3) the demonstration of the efficacy of combining a GSC cytotoxic drug and a differentiation-inducing drug. The results from this project demonstrated that RFC-1 expression, which is critically involved in folate metabolism, was upregulated in GSCs and that methotrexate, an anti-folate metabolite, had cytotoxic activity toward GSCs and showed combinatorial activity with CEP1347 as a differentiation-inducing drug. The results also demonstrated phospholipase Cε overexpressed in GSCs maintained their stemness through JNK and as such could possibly be an excellent target to selectively block the JNK pathway in GSCs.

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。本課題では特に前課題（18H02908）をキッカケとして着目するようになった、悪性脳腫瘍のがん幹細胞が持つ「アキレス腱」に関する研究をさらに展開した。その結果悪性脳腫瘍の新たな治療標的・治療戦略を見出すことに成功し、本課題の成果は悪性脳腫瘍の治療成績の改善に大きく貢献することが期待される。