Development of new therapeutic agents targeting Rac1-GSPT1 axis in glioma
Project/Area Number |
18K16584
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Kobe University |
Principal Investigator |
Ishii Taiji 神戸大学, 医学研究科, 医学研究員 (80622167)
|
Project Period (FY) |
2018-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | Glioblastoma / GSPT1 / Glioma / glioma / グリオーマ / cereblon |
Outline of Final Research Achievements |
GSPT1 is a downstream molecule of Rac1 and is an important molecule that regulates the cell cycle. The antitumor effect of CC-885, a cereblon-binding molecule recently reported as a GSPT1 inhibitor, was analyzed using glioma cells. There was no relationship between the expression level of GSPT1 and prognosis in malignant glioma. When CC-885 was added to glioma cells, GSPT1 protein expression was markedly reduced and cell proliferation was also suppressed. When CC-885 was administered to a mouse brain transplant model, tumor growth was suppressed in the brain, apoptosis was increased, and the survival time of the mice was significantly prolonged. Based on the above, CC-995 showed high antitumor activity against glioma cells, suggesting the possibility of becoming a new therapeutic agent.
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Academic Significance and Societal Importance of the Research Achievements |
膠芽腫を始めとする悪性グリオーマは未だ有効な治療方法がない非常に予後不良な脳腫瘍で、新たな治療ターゲットが切望されている。本研究では、細胞周期調節因子のGSPT1に着目した。まず、GSPT1がグリオーマ組織で高度に発現していることが確認された。また、セレブロン結合分子で最近GSPT1阻害剤として報告されたCC-885をマウスのグリオーマ細胞脳移植モデルに投与すると、著明な抗腫瘍効果を示したことから、GSPT1阻害はグリオーマに対する新たな治療ターゲットとして有望であることが示された。今後、GSPT1をターゲットとした新たな薬剤も開発されてくることが期待される。
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Report
(3 results)
Research Products
(2 results)