2016 Fiscal Year Final Research Report
Development of novel therapy with inhibition of Notch signaling for glioma stem cells
| Project/Area Number |
15K19980
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurosurgery
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| Research Institution | Toho University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 神経膠腫 / グリオーマ幹細胞 / 神経膠芽腫 / Notch / 新規治療 / 分子標的治療 |
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| Outline of Final Research Achievements |
The Notch signaling is an evolutionarily conserved pathway that plays an important role in multiple cellular processes. We investigated the effects of Notch inhibition in glioma stem cell (GSC) populations using γ secretase inhibitors. Drug cytotoxicity testing showed differential growth responses to the inhibitors. Responder GSCs had an enriched proneural gene signature in comparison to nonresponders. Analysis of TCGA dataset identified a group (43.9%) of tumors with proneural signature showing high Notch pathway activation. Inhibition of Notch pathway by γ secretase inhibitor treatment attenuated proliferation and self-renewal of responder GSCs and induces both neuronal and astrocytic differentiation. Our results suggest that proneural GBM characterized by high Notch pathway activation may exhibit greater sensitivity to γ secretase inhibitor treatment, holding a promise to improve the efficiency of current glioma therapy.
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| Free Research Field |
脳神経外科学
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