2022 Fiscal Year Final Research Report
Genetic abnormalities in malignant pleural mesothelioma and its clinical application to personalized therapy
Project/Area Number |
19K08664
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53030:Respiratory medicine-related
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Research Institution | Keio University |
Principal Investigator |
KAWADA Ichiro 慶應義塾大学, 保健管理センター(日吉), 准教授 (00327503)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 悪性胸膜中皮腫 / オルガノイド / 薬剤感受性 / Precision medicine |
Outline of Final Research Achievements |
The aim of this study is to develop new therapeutic agents and clinical applications for individualized treatment for malignant pleural mesothelioma (MPM) patients with a severe prognosis. We succeeded in establishing an MPM model using an organoid, which is an organ made in vitro three-dimensionally. At present, 9 cases have been stably established. We are going to strive to understand molecular abnormalities using RNA-seq. We are currently proceeding with genome sequencing using the established organoids, and found that each line has MPM-specific gene mutations. Principal component analysis (PCA) was performed from RNA-seq data, and MPM showed a different distribution from adenocarcinoma, squamous cell carcinoma, small cell lung cancer, normal alveoli, and airway epithelium. Furthermore, in order to confirm the homology with the original patient tissue, we are conducting immunostaining of organoids and verification with Xenograft models.
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Free Research Field |
肺癌,悪性中皮腫の遺伝子異常
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Academic Significance and Societal Importance of the Research Achievements |
分子シグナル伝達経路を標的とした新たな治療探索のため、樹立したMPMオルガノイドでRNA-seqを用いてその分子異常の把握に努める。そして、MPMにおけるMETシグナル経路異常などの生物学的意義を検証する。これにより、治療に伴うMPMの分子進化を把握し、化学療法や免疫治療に対する耐性化機序などを同定できる可能性がある。正常細胞からも樹立できるという利点から、正常細胞への毒性を考慮に入れた患者毎の薬剤スクリーニング系の構築の可能性がある。一人一人の患者の治療効果予測にオルガノイドモデルを用いることで、Precision Medicineへの応用が期待される。
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