Development of anti-cancer drug evaluation method using human pancreatic organoids with microenvironment

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10517
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: The University of Tokyo (2019); Yokohama City University (2017-2018)
• Principal Investigator: Ueno Yasuharu 東京大学, 医科学研究所, 特任助教 (60375235)
• Co-Investigator(Kenkyū-buntansha): 谷口 英樹 東京大学, 医科学研究所, 教授 (70292555)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 癌オルガノイド / 癌微小環境 / 治療抵抗性 / 薬剤評価

Outline of Final Research Achievements

To establish a drug sensitivity evaluation system that reproduces the high drug resistance in human pancreatic cancer, we have developed a method for reconstructing human cancer organoids with a cancer microenvironment and a drug evaluation method. When a human pancreatic cancer cell line was three-dimensionally co-cultured with vascular endothelial cells and mesenchymal cells, a cancer tissue (organoid) with abundant stroma was reconstituted. A human pancreatic cancer cell line containing a luciferase gene was used to reconstruct a pancreatic cancer organoid with a stroma for drug sensitivity evaluation. Cancer organoids showed higher drug resistance than cell aggregates consisting of cancer cells alone, suggesting that the cancer microenvironment was reconstituted. We show that cancer organoids containing stroma are useful for modelling drug resistance in pancreatic cancer.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

膵癌は予後不良な難治癌であり、新たな治療法の確立が急務である。膵癌に有効な薬剤開発を進めるためには膵癌の高い薬剤抵抗性を再現しうる評価系が必要不可欠であるが、薬剤耐性に関与する癌微小環境を人為的に再現する手法が確立されていない課題がある。本研究において確立した間質を有するヒト膵癌オルガノイドの再構成技術は、膵癌の精度の高い薬剤評価に有益と考えられ、膵癌の創薬開発が促進されることが期待される。