Elucidation of the molecular mechanism of development of anaplastic thyroid cancer using gene mutation analysis and comprehensive gene expression analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Shinshu University
• Principal Investigator: Ito Ken-ichi 信州大学, 学術研究院医学系, 教授 (10334905)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 甲状腺未分化癌 / 稀少癌 / 新規治療戦略 / 分子標的薬 / 薬剤耐性機構

Outline of Final Research Achievements

To develop a novel therapeutic strategy for anaplastic thyroid cancer (ATC), we analyzed the sensitivity of lenvatinib, a multi-targeted tyrosine kinase inhibitor (MKI) indicated for ATC in Japan, to the ATC-derived cell line FRO and obtained the following results. (1) Lenvatinib treatment activates EGFR phosphorylation in FRO cells. (2) The combination of lenvatinib and an EGFR inhibitor synergistically inhibits FRO cell proliferation in vitro. (3) In a mouse model of FRO cell transplantation, the combination of lenvatinib and an EGFR inhibitor significantly increased apoptosis of cancer cells and significantly inhibited tumor growth compared to lenvatinib alone. These results suggest that the combination of lenvatinib and an EGFR inhibitor may be a novel therapeutic strategy for ATC.

Free Research Field

外科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では、極めて予後不良な難治性悪性腫瘍である甲状腺未分化癌が、本邦で承認されている分子標的薬に対し耐性を示す機序の一部を解明した。既存の分子標的薬を用いた方法で耐性の克服が一部可能であり、臨床応用の可能性が期待できる。難治性の稀少癌である未分化癌に対する新規治療戦略を創出できたことは、意義が大きいと考えられる。