| Project/Area Number |
17K16533
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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 |
Digestive surgery
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| Research Institution | National Cancer Center Japan (2018)
The University of Tokyo (2017) |
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Principal Investigator |
Noguchi Rei 国立研究開発法人国立がん研究センター, 研究所, 研究員 (30779682)
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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 | 腹膜偽粘液腫 / 全ゲノムシークエンス / RNA-Seq / トランスジェニックマウス / ゼノフラフト / 希少がん / 動物モデル / ゲノム / マウスモデル / 網羅的発現解析 |
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| Outline of Final Research Achievements |
Pseudomyxoma peritonei (PMP) is a rare disease with distinct feature caused by cancerous cells producing mucin. Although mutations of KRAS and GNAS have been involved in carcinogenesis of PMP, druggable targets based on gene expression profiles and genomic profiles have been unknown. Additionally, there was no animal model for PMP due to its rarity. To disclose druggable targets for PMPs,comprehensive genome analysis consisting of RNA-sequencing and whole genome sequencing was conducted with PMP tissues and their matched normal tissues. Cre recombinant mice were crossed with Kras mutant mice and GNAS mutant mice. The genomic analysis reveals that PI3K-AKT pathway is identified as a new druggable target and mucin producing related genes and inflammation related genes play important role for tumorigenesis of PMP. Not only GNAS mutation but also mutations of GNAS and KRAS enable mice to generate appendiceal polyps. However, these polyps did not show PMP-unique phenotype, mucin producing.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は希少性から新薬開発を行うのが難しく、既存の治療薬のみしか使われていない腹膜偽粘液腫の臨床に役立てるための研究を行うことである。本研究の網羅的ゲノム解析により新たな治療標的としてPI3K-AKT pathwayが同定された。同定したパスウェイを阻害する既存薬の治療への応用の可能性が広げられた。この悲惨な希少がんの治療を改善させ、予後も改善することが示唆される。
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