Study of osimertinib resistance mechanism against EGFR-positive lung adenocarcinoma using PDX model

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08141
• 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): 2018-04-01 – 2021-03-31
• Keywords: PDX / 肺がん / EGFR変異 / Osimertinib / オシメルチニブ耐性

Outline of Final Research Achievements

A PDX model was established in 3 patients diagnosed with lung adenocarcinoma. We compared the tumors engrafted with surgically resected tumors (SRT) and PDX models by H & E staining and immunostaining, and confirmed that the histological type (degree of differentiation, interstitial mass) was maintained. In case # 11, treatment with osimertinib was so successful that we were unable to induce resistance because the tumor disappeared. On the other hand, in case # 7, we succeeded in making osimertinib resistant in about 100 days and established a PDX model of osimertinib resistance. From the above results, it was possible to establish the PDX model system, which was the original purpose, and to apply the PDX model to the therapeutic effect determination of EGFR inhibitors.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

前臨床モデルであるヒトがん細胞株を用いた研究においては、患者の腫瘍が本来有している腫瘍組織微小環境や腫瘍不均一性が欠如しており、実臨床との薬剤感受性の乖離がしばしば問題となる。しかし、本研究で作製に成功したPDXモデルでは患者組織を反映しており、治療薬のスクリーニング、薬剤耐性研究に活用できる。さらに、PDXモデルを利用し解析することにより、肺がんの再発あるいはEGFR阻害薬耐性となった患者に新たな治療薬を提案でき、肺がん患者の予後改善につながることが期待され、本研究成果は社会的に意義がある。