2021 Fiscal Year Final Research Report

Development of a new treatment strategy for HER2-alterated lung cancer

Research Project

PDF

Project/Area Number	19K09285
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55040:Respiratory surgery-related
Research Institution	Kindai University
Principal Investigator	Soh Junichi 近畿大学, 医学部, 教授 (90559890)
Co-Investigator(Kenkyū-buntansha)	冨田秀太岡山大学, 大学病院, 准教授 (10372111) 豊岡伸一岡山大学, 医歯薬学総合研究科, 教授 (30397880) 山本寛斉岡山大学, 大学病院, 講師 (40467733) 阪口政清岡山大学, 医歯薬学総合研究科, 教授 (70379840) 光冨徹哉近畿大学, 医学部, 教授 (70209807) 須田健一近畿大学, 医学部, 講師 (30631593) 諏澤憲岡山大学, 大学病院, 助教 (90839713)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	HER2 / 肺癌 / 薬剤耐性 / ERBB2
Outline of Final Research Achievements	We conducted sensitivity testing and investigated the mechanism of acquired resistance using lung, gastric, and breast cancer cell lines for several HER2-targeting agents, and reported the results in several English papers. In addition, we confirmed the sensitivity of a novel HER inhibitor, Tarloxotinib, and identified a new resistance-related mutation, HER2 exon C805S, involved in resistance using Ba/F3 cells transfected with HER2 mutation, which was reported in an English paper. A new afatinib-sensitive HER2 mutation spectrum identified in the LUX-Lung8 study, which evaluated the efficacy of the EGFR/HER2 inhibitor afatinib in patients with squamous cell lung cancer, was introduced into the Ba/F3 cell line and its pathogenicity and drug sensitivity were investigated and reported in an English paper.
Free Research Field	呼吸器外科、肺癌分子生物学
Academic Significance and Societal Importance of the Research Achievements	HER2異常肺癌の頻度は5%程度であるが、HER2異常は複数の癌腫で認められ、HER2標的療法は個別化治療として期待される。HER2異常スペクトル別にHER2標的薬の効果とその獲得耐性の克服を検討することで、HER2異常肺癌に対するプレシジョン・メディシンの確立を目指した基礎的検討を実施した。HER2異常細胞株を用いて、複数のHER2標的薬の効果を検討し、長期暴露による薬剤耐性株や人工的なHER2変異導入細胞株の樹立により、耐性機序の解明とその治療法の開発を行い、複数の報告を行っている。