Development of biliary and pancreatic tumor cell bank using organoid culture and its application to personalized therapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03592
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Keio University
• Principal Investigator: Saito Yoshimasa 慶應義塾大学, 薬学部(芝共立), 准教授 (90360114)
• Project Period (FY): 2017-04-01 – 2020-03-31
• 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

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.

Free Research Field

腫瘍治療学

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。