Establishment of strategy for the treatment of lung cancer harboring rare mutations

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03671
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: University of Yamanashi (2021-2022); Keio University (2019-2020)
• Principal Investigator: Soejima Kenzo 山梨大学, 大学院総合研究部, 教授 (30236145)
• Co-Investigator(Kenkyū-buntansha): 浜本 純子 慶應義塾大学, 医学部(信濃町), 助教 (40570239) ; 安田 浩之 慶應義塾大学, 医学部(信濃町), 准教授 (70365261)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肺癌 / 稀な遺伝子変異 / EGFR遺伝子変異 / 医師主導治験 / オルガノイド

Outline of Final Research Achievements

Lung cancer is the leading cause of cancer deaths. With the recent rapid development of molecular biological analysis, various driver gene mutations have been discovered, and molecularly targeted therapies have been developed, leading to significant improvement in prognosis. However, effective treatments have not yet been developed due to the small number of cases with rare gene mutations. In this study, we revealed that in Japanese patients with EGFR mutations, EGFR exon 20 insertion gene mutations account for about half of these cases. We developed an in silico sensitivity prediction system for optimal drug selection and showed in clinical trials that we can predict the progression-free survival of each case based on individual genetic mutation type and drug concentration in the blood. These findings are important for implementing truly personalized medicine and have high academic and social significance for promoting future drug development for other rare genetic abnormalities.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

これまで単に遺伝子変異としてしか認識されていなかった稀な遺伝子変異の多くが治療標的となり得るドライバー変異であり、日本人のEGFR変異においては5.5％を占め、特にEGFRエクソン20挿入遺伝子変異はその約半数を占めており、薬剤開発が急務であることを明らかにした。さらに最適な薬剤選択のためのin silicoでの感受性予測システムを開発し、臨床試験においては個々の遺伝子変異型および薬剤の血中濃度により各症例の無増悪生存を予測できることを明らかにした。これらの知見は真の個別化治療を実践する上で重要であり、今後の他の稀な遺伝子異常に対する薬剤開発の推進において高い学術的および社会的意義を有する。