The effect of the Notch inhibitor and a preclinical study for glioma stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861263
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: TANAKA Shingo 金沢大学, 医学系, 協力研究員 (40507084)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 膠芽腫 / MRK-003 / Notch阻害剤 / グリオーマ幹細胞

Outline of Final Research Achievements

Glioblastoma is the most malignant primary brain tumor in humans. The patients with glioblastoma have a uniformly poor prognosis. The significance of targeting glioblastoma-initiating cells (GICs) may be important for successful treatment of glioblastoma. In this study, we analyzed the effect of the Notch inhibitor MRK-003 on nine patient-derived GICs. MRK-003 suppressed GIC's proliferation and stemness maintenance, and promoted their apoptosis. Based on their sensitivities to MRK-003, the nine GICs were divided into “relatively sensitive” and “relatively resistant” GICs. The IC50(half maximal inhibitory concentration) of MRK003 in a set of GICs exhibited a negative correlation with CD44 and positive correlation with CD133. Our study suggested that MRK-003 may exhibit significant therapeutic potential for GICs with CD44-high and CD133-low expression.

Free Research Field

脳神経外科学