Establishment of new therapeutic strategy using afatinib in canine head and neck squamous cell carcinoma.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20619
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: Azabu University (2022); Nippon Veterinary and Life Science University (2021)
• Principal Investigator: Miyamoto Ryo 麻布大学, 大学病院, 特任助手 (30822580)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 扁平上皮癌 / 犬 / アファチニブ / 分子標的療法 / 株化細胞 / 増殖機構 / ドライバー / EphB3

Outline of Final Research Achievements

Afatinib showed the strongly cell growth inhibition activity in canine tonsil squamous cell carcinoma cell line. In this study, a new therapeutic target of afatinib, EphB3, was identified. In afatinib-sensitive cell line, high expression of EphB3 and Ephrin-B2, and enhanced phosphorylation of EphB3 were observed among six canine squamous cell carcinoma cell lines. No EphB3 or Ephrin-B2 mRNA mutation was found in nucleotide analysis. In contrast, analysis of interaction between EphB3 and Ephrin-B2 showed that Ephrin-B2 induced directly enhanced phosphorylation of EphB3, and which played an important role in the growth of afatinib-sensitive cell line. In a clinical trial of afatinib, tumor shrinkage was found in one of five canine squamous cell carcinoma cases.

Free Research Field

がん分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では人の肺がん治療薬であるアファチニブが一部の犬の扁平上皮癌細胞の増殖を強く抑制することを明らかにした。さらにアファチニブの作用機序は従来のものと異なり、新規標的分子であるEphB3を標的とすることを示した。今回明らかとなった扁平上皮癌細胞の増殖機構およびアファチニブ抑制機構の解明は、犬扁平上皮癌および人肺がんにおける新たな治療戦略の確立に発展する重要なデータと考えられる。