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A new treatment targeting 2HG induced mitochondrial dysfunction in IDH-mutant gliomas

Research Project

Project/Area Number 17K16631
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionNiigata University

Principal Investigator

Abe Hideaki  新潟大学, 脳研究所, 非常勤講師 (80783331)

Research Collaborator Natsumeda Manabu  
Okada Masayasu  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
KeywordsIDH / グリオーマ / 2-HG / ミトコンドリア / 免疫染色 / Glioma / 神経膠腫
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.

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。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (2 results)

All 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas and MGMT Silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas2018

    • Author(s)
      Hideaki Abe, Manabu Natsumeda, Yu Kanemaru, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Junichi Yoshimura, Makoto Oishi, Yukihiko Fujii
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 58 Issue: 7 Pages: 290-295

    • DOI

      10.2176/nmc.ra.2018-0044

    • NAID

      130007405002

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] H3 K27M-mutant DMG細胞におけるMGMT発現解析及びTMZ耐性機序の検討2018

    • Author(s)
      阿部英明
    • Organizer
      第18回日本分子脳神経外科学会
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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