Exploration of diagnostic markers targeting early-stage lesions of pancreatic carcinogenesis using novel organoid models.
| Project/Area Number |
18K07932
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Izumiya Masashi 東京大学, 大学院医学系研究科(医学部), 講師 (90532739)
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| Co-Investigator(Kenkyū-buntansha) |
筆宝 義隆 千葉県がんセンター(研究所), 発がん制御研究部, 研究所長 (30359632)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 膵がん / オルガノイド / 発がんモデル / スクリーニング / 早期診断マーカー / オルガノイドモデル / IPMN / PanIN |
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| Outline of Final Research Achievements |
In this study, we aimed to find the results that can improve the prognosis of pancreatic cancer by using a model that recapitulates the pancreatic carcinogenesis process using organoids. First, we introduced mutations such as Kras and p53 KO into normal pancreatic organoids of mice, transplanted subcutaneously into nude mice, and pathologically evaluated tumorigenic potential and tumors.Tumors corresponding to PanIN were formed by the Kras mutation alone.Tumors with a higher degree of atypia were formed when we introduced mutations such as p53 in addition to the Kras mutation. Next, this model was used to screen for drugs that inhibit tumor organoid growth. After screening about 400 compounds from the drug library, we identified several compounds that exhibited growth inhibition.
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| Academic Significance and Societal Importance of the Research Achievements |
膵がんは代表的な難治性の固形がんであり、依然としてその予後は不良である。オルガノイドを用いた膵発がんモデルは、比較的短期間でヒトの膵がんに類似した病理組織像を持つ腫瘍の形成が可能であり、新規の治療法開発の基盤としての有用性が示された。また、Kras, p53の変異には特異的な阻害薬に乏しく、これらを有する腫瘍を抑制する候補薬が同定されたことは、新規治療標的につながるものとして有意義であると言える。
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Report
(6 results)
Research Products
(3 results)
