Development of biliary and pancreatic tumor cell bank using organoid culture and its application to personalized therapy
Project/Area Number |
17H03592
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Tumor diagnostics
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Research Institution | Keio University |
Principal Investigator |
Saito Yoshimasa 慶應義塾大学, 薬学部(芝共立), 准教授 (90360114)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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Keywords | 胆道がん / 膵臓がん / オルガノイド / ドラッグ・リポジショニング / 抗真菌薬 / 胆道・膵臓がん / ドラッグリポジショニング / 既存薬 / オルガノイド培養 / 個別化治療 / がんの個性診断 |
Outline of Final Research Achievements |
We successfully established organoids derived from biliary tract carcinoma (BTC) patients. These BTC organoids were cultured stably for over one year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Gene expression profiling of the organoids and clinical data of patients revealed that SOX2, KLK6, and CPB2 could be a potential prognostic biomarker for patients with BTC. Moreover, we performed a drug screening with a compound library consisting of drugs employed clinically for their ability to suppress BTC organoids as a “drug repositioning” strategy. We discovered that the antifungal drugs amorolfine and fenticonalzole significantly suppressed the growth of BTC organoids. Antifungal drugs including amorolfine and fenticonalzole could be potentially applied for the prevention and treatment of BTC patients.
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Academic Significance and Societal Importance of the Research Achievements |
この研究成果についてプレスリリースを行なったところ、非常に大きな反響があり、多くの末期胆道がんの患者さんより、手紙やメールなどで直接問い合わせがあった。いずれも現行の治療で効果がなく、抗真菌薬の投与を試してみたい、または、もし治験が始まっているのであれば、是非エントリーしたいとのことであった。今後は、今回のスクリーニングにより特定された抗真菌薬や脂質異常症治療薬を基盤とした低分子化合物に関する基礎研究をさらに進め、動物実験、非臨床Proof of Concept (POC) の取得、医師主導治験を経て、可能な限り早く、胆道・膵臓がんに対する新たな治療薬の創出につなげていきたいと考えている。
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma.2019
Author(s)
Saito Y, Muramatsu T, Kanai Y, Ojima H, Sukeda A, Hiraoka N, Arai E, Sugiyama Y, Matsuzaki J, Uchida R, Yoshikawa N, Furukawa R, Saito H.
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Journal Title
Cell Rep
Volume: 27
Issue: 4
Pages: 1265-1276
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genomic Profiling of Biliary Tract Cancer Cell Lines Reveals Molecular Subtypes and Actionable Drug Targets.2019
Author(s)
Lau DK, Mouradov D, Wasenang W, Luk IY, Scott CM, Williams DS, Yeung YH, Limpaiboon T, Iatropoulos GF, Jenkins LJ, Reehorst CM, Chionh F, Nikfarjam M, Croagh D, Dhillon AS, Weickhardt AJ, Muramatsu T, Saito Y, Tebbutt NC, Sieber OM, Mariadason JM.
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Journal Title
iScience
Volume: 21
Pages: 624-637
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma.2019
Author(s)
Chuma M, Toyoda H, Matsuzaki J, Saito Y, Kumada T, Tada T, Kaneoka Y, Maeda A, Yokoo H, Ogawa K, Kamiyama T, Taketomi A, Matsuno Y, Yazawa K, Takeda K, Kunisaki C, Ogushi K, Moriya S, Hara K, Nozaki A, Kondo M, Fukuda H, Numata K, Tanaka K, Maeda S, Sakamoto N.
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Journal Title
Hepatology Research
Volume: 49
Issue: 7
Pages: 810-822
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Establishment of patient-derived organoids and drug screening for biliary tract carcinoma2019
Author(s)
Saito Yoshimasa, Muramatsu Toshihide, Kanai Yae, Ojima Hidenori, Sukeda Aoi, Hiraoka Nobuyoshi, Arai Eri, Sugiyama Yuko, Matsuzaki Juntaro, Uchida Ryoei, Yoshikawa Nao, Furukawa Ryo, Saito Hidetsugu
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells.2018
Author(s)
Murakami Y, Sugiyama K, Ebinuma H, Nakamoto N, Ojiro K, Chu PS, Taniki N, Saito Y, Teratani T, Koda Y, Suzuki T, Saito K, Fukasawa M, Ikeda M, Kato N, Kanai T, Saito H.
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Journal Title
BMC Cancer.
Volume: 3
Issue: 1
Pages: 680-680
DOI
Related Report
Peer Reviewed / Open Access
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