Novel therapeutic approaches for lung cancer by using iPS cell-derived organoids

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17748
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Okayama University
• Principal Investigator: Shien Kazuhiko 岡山大学, 大学病院, 講師 (30708079)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 非小細胞肺がん / 微小環境 / オルガノイド / iPS細胞

Outline of Final Research Achievements

In this study, we generated a unique lung cancer organoid model by combining lung tissue differentiated in 3D from human pluripotent stem cells (lung organoids) and genome editing technology, and examined its validity as a pathological model to develop novel therapeutic strategies targeting cancer cells and their surrounding cancer microenvironment. After generating lung organoids using human pluripotent stem cells, we successfully recapitulated precancerous lesion-like changes and the early tumorigenesis process of lung adenocarcinoma by combining overexpression of oncogenes and loss of tumor suppressor genes. These cells showed characteristic drug sensitivity to molecular targeted therapies, providing new insights into overcoming drug treatment resistance.

Free Research Field

呼吸器外科

Academic Significance and Societal Importance of the Research Achievements

従来、肺がんの腫瘍形成過程をヒト由来の細胞を用いて3次元的に再現することは困難であった。本研究では、ヒト多能性幹細胞と新たな遺伝子編集手法を用いることで、「肺オルガノイド（多能性幹細胞から3次元で分化誘導した肺組織）をがん化させる」ことに成功した。今回の新たな3次元肺がんモデルを用いることで、肺発がん機序の解明のみならず、肺がん細胞および周囲のがん微小環境を標的とした新規治療薬開発への応用が期待される。