A new treatment targeting 2HG induced mitochondrial dysfunction in IDH-mutant gliomas
| Project/Area Number |
17K16631
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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 | Niigata University |
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Principal Investigator |
Abe Hideaki 新潟大学, 脳研究所, 非常勤講師 (80783331)
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| Research Collaborator |
Natsumeda Manabu
Okada Masayasu
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | IDH / グリオーマ / 2-HG / ミトコンドリア / 免疫染色 / Glioma / 神経膠腫 |
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| Outline of Final Research Achievements |
Mutations of isocitrate dehydrogenase (IDH) genes are frequently found in malignant gliomas. These mutations produce the oncometabolite 2-hydroxyglutarate (2-HG), which is thought to cause gliomagenesis. However, it is also known that IDH-mutant gliomas have relatively good prognoses. We hypothesized that 2-HG produced by IDH-mutant gliomas accumulate inside mitochondria, causing mitochondrial dysfunction to IDH-mutant gliomas. IDH mutant inhibitors, which inhibit 2-HG, may actually be beneficial to IDH-mutant glioma cells. We set out to prove this hypothesis. While we could not prove this hypothesis within the funding period, but this notion could cause a paradigm shift in the treatment of IDH-mutant gliomas.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性神経膠腫は極めて予後不良な脳腫瘍で、未だ根本的治療法は編み出されていない。悪性神経膠腫に高頻度に認められるイソクエンサン脱水素（IDH）変異に対する阻害剤が開発されたが、臨床ではその有効性は証明されておらず、ある研究ではIDH阻害剤を投与した方が腫瘍の増殖が速くなる事さえ解っている。本研究ではIDH変異型悪性神経膠腫に対して何故、IDH阻害剤が無効なのかに迫った、大変意義深い研究である。
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Report
(3 results)
Research Products
(2 results)
