Highly efficient establishment of lung cancer patient-derived organoids and its application for prediction of sensitivities to various treatments

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03773
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kindai University
• Principal Investigator: Mitsudomi Tetsuya 近畿大学, 医学部, 教授 (70209807)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肺癌 / オルガノイド / 薬剤感受性試験 / ドライバー遺伝子 / 分子標的治療 / 腫瘍微小環境

Outline of Final Research Achievements

We established a method for creating lung tumor organoids (LTO) from surgically resected lung cancer specimens and characterized them in various ways in search for their clinical applications. We were able to establish 53 LTOs from 79 lung cancer patients, and they accurately reflected the characteristics of the parent tumors in terms of morphology, protein expression, and gene alterations. The success rate was lower for squamous cell carcinoma. The ability for long-term passaging was associated with poor prognosis. We detected seven driver mutations in both LTOs and parent tumors, including one EGFR exon 20 insertion mutation (H773delinsYNPY) which is usually refractory to currently available drugs. However, as this LTO showed sensitivity to osimertinib, the patient was treated with osimertinib, resulting in significant clinical response. These results suggest that LTOs could be a useful tool for developing treatment strategies.

Free Research Field

呼吸器外科学、腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究においては、従来、消化器癌とくらべて樹立が困難とされてきた非小細胞肺癌において、67％の症例からオルガノイドを樹立できたことは臨床応用を考えた上で意義深い。また、これらのオルガノイドは病理組織学的特徴およびほとんどの遺伝子変化を維持しており、薬物感受性の前臨床的評価に有用であることが期待される。実際、まれなEGFRエクソン20挿入変異を有する患者においてはオルガノイドの薬剤感受性結果に基づいてシメルチニブを投与することで、高い抗腫瘍効果がえられ、臨床的な有用性を示せた。これらのことは学術的、臨床的に意義深いと思われる。