2020 Fiscal Year Final Research Report
Identification of molecular targets by analysis of signaling networks in pancreatic cancer
| Project/Area Number |
16H05165
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tohoku University (2017-2020)
Tokyo Women's Medical University (2016) |
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Principal Investigator |
Furukawa Toru 東北大学, 医学系研究科, 教授 (30282122)
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| Co-Investigator(Kenkyū-buntansha) |
樋口 亮太 東京女子医科大学, 医学部, 講師 (20318059)
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| Project Period (FY) |
2016-04-01 – 2021-03-31
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| Keywords | 膵臓癌 / 膵頭領域癌 / オルガノイド / 全エクソン解析 / 分子標的 / ドライバー分子 / インテグリン結合キナーゼ |
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| Outline of Final Research Achievements |
We aimed to establish a system for identifying and testing genotype-oriented targeted drugs for pancreatobiliary cancers by combining exome sequencing and organoid culture of primary tumors. Tumor cells isolated from resected tumors were subjected to organoid cultures. Exome sequencing was performed on the primary tumors. Genotype-oriented candidate targeted drugs were identified from the exome sequencing and their efficacies were tested in the organoids. Organoid cultures were succeeded in 30 of 54 (55.6%) cases. Exome sequencing revealed a variety of somatic mutations. Some of the aberrations were candidates for targeted therapies. Integrin-linked kinase (ILK) was a novel candidate target, and an ILK inhibitor was confirmed to suppress proliferation of patient-derived organoids. By combining exome sequencing and organoid culture, our model enabled to identify genotype-oriented targets for personalized medicine and to test efficacies of candidate targeted drugs in the organoids.
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| Free Research Field |
人体病理学、実験病理学、腫瘍学、遺伝学、分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
癌の診療では腫瘍のゲノム解析から個々の癌に適した分子標的を見出し治療することが行われるが、見出した分子標的が実際に患者由来の癌に対し効果を示すか検証できるシステムがなかった。本研究では難治性である膵臓・膵頭領域癌について、癌オルガノイド培養と網羅的遺伝子解析を組み合わせることにより、実際に患者由来検体で分子標的治療の効果を確認できる個別化医療システムを構築した。また、膵臓・膵頭領域癌に対する新規分子治療標的としてILKを同定した。
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