Lung adenocarcinoma organoids to overcome drug resistance

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kanazawa University
• Principal Investigator: Kita Kenji 金沢大学, がん進展制御研究所, 特任助手 (80625252)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肺がん / オルガノイド / オシメルチニブ / 薬剤耐性

Outline of Final Research Achievements

Two organoids were established from the PDX model, and two lung adenocarcinomas and one mucinous adenocarcinoma were successfully established from surgical specimens. Drug sensitivity testing of osimertinib resistant organoids established from the PDX model showed that afatinib and the HDAC inhibitor, quisinostat, were highly effective. Whole genome sequencing was performed on osimertinib resistant organoid DNA. The results showed that 70~80% of the DNA was derived from mice, indicating that considerable caution should be exercised when establishing organoids from PDX models due to the presence of mouse cells.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

オルガノイドは3次元であるため、2次元培養の細胞株に対して、より組織を反映しているという特色がある。しかし、肺がんに至ってはオルガノイド培養に関する報告が少なく、まだ開発段階である。以上の背景により、肺がんオルガノイドを樹立し、培養法を確立することは、薬剤耐性メカニズムの評価に有用と考えられ、肺がんオルガノイドを樹立することによる有効な新規治療法の開発は学術的意義、社会的意義があると思われる。