Investigation on anticancer drugs-induced epithelial-mesenchymal transition for development of preventive approach to drug-induced lung injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16447
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Hiroshima University
• Principal Investigator: Kawami Masashi 広島大学, 医系科学研究科(薬), 助教 (20725775)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 薬剤性肺障害 / 上皮間葉転換 / セルソーティング / バイオインフォマティクス / 抗がん剤 / メトトレキサート / p53

Outline of Final Research Achievements

Chemotherapeutic drugs often induces serious lung diseases as a adverse drug reaction, which is triggered by epithelial-mesenchymal transition (EMT) in injured alveolar epithelial cells. However, few mechanistic studies focusing on the drug-induced EMT is performed. The present study aimed to clarify the molecules specifically involved in anticancer drug-induced EMT.
In this study, several factors such as Nrf2, ITGA2, and p53 were closely associated with EMT induced by methotrexate (MTX), a popular chemotherapeutic agent. In particular, p53 contributed to MTX-induced EMT, but not antitumor effects, which would provide a perspective that p53 may be a one of specific molecules specifically associated with MTX-induced EMT.

Free Research Field

生物薬剤学、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた知見は、これまで不明であった薬物誘発性上皮間葉転換機構の一端を解明したものであり、肺線維症をはじめとした上皮間葉転換に関連する副作用の発症を予防しながら抗がん剤治療の継続が望める画期的な治療法の構築に資する有用な基礎的知見になると考えられる。