Drag repositioning for malignant glioma targeting glioma stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293322
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: Nakada Mitsutoshi 金沢大学, 医学系, 教授 (20334774)
• Co-Investigator(Renkei-kenkyūsha): HIRAO Atsushi 金沢大学, がん進展制御研究所, 教授 (90343350) ; MINAMOTO Toshinari 金沢大学, がん進展制御研究所, 教授 (50239323)
• Research Collaborator: DONG Yu ; FURUTA Takuya ; SABIT Hemragul ; KITABAYASHI Tomohiro
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: グリオーマ / 幹細胞 / ドラッグリポジショニング

Outline of Final Research Achievements

Glioma stem cell (GSC)-targeted therapy is a promising approach to treat patients with glioblastoma (GBM). Here, we identified fluspirilene, a traditional antipsychotic drug, as a GSC-targeting agent, selected from thousands of existing drugs with the purpose of drug repositioning. We initially screened drug libraries for small-molecule compounds showing a greater efficacy in inhibiting the proliferation and survival of different GSC lines. Drugs already reported to show therapeutic effects against GBM or those under clinical trials were excluded from subsequent screening. Among the candidate drugs, fluspirilene demonstrated a significant inhibitory effect on the proliferation and invasion of glioma cells as well as in the model mice treated with the drug. These effects were associated with the inactivation of the signal transducer and activator of transcription 3 (STAT3). Redeveloping of fluspirilene is a promising approach for the treatment of GBM.

Free Research Field

脳腫瘍学