Development of a novel treatment for anaplastic thyroid carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07211
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Tohoku University
• Principal Investigator: Saijo Ken 東北大学, 大学病院, 助教 (70636729)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 甲状腺未分化癌 / レンバチニブ / 阻害剤ライブラリー

Outline of Final Research Achievements

Anaplastic thyroid carcinoma (ATC) is an aggressive cancer. Although lenvatinib is the only therapeutic agent, its efficacy is insufficient. To develop the novel treatment for ATC, we used SCADS inhibitor kits to screen compounds that could potentiate the anti-proliferative effect of lenvatinib on the ATC cell. As a result, IRAK 1/4 Inhibitor I was identified. The combination effect of lenvatinib and IRAK1/4 inhibitor I was investigated in four ATC cell lines, and the synergistic anti-cell proliferation effect was observed. Cell cycle analysis showed that IRAK1/4 Inhibitor I potentiated lenvatinib-induced cell cycle arrest in G2/M phase. Knockdown of IRAK1/4 gene similarly potentiated the anti-proliferative effect of lenvatinib. The combination of lenvatinib and IRAK1/4 inhibitor I showed more potent anti-tumor effect than control and monotherapy of each drug in xenograft mouse model. IRAK1/4 inhibitor I was identified as a promising drug to potentiate the effect of lenvatinib in ATC.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

進行が極めて速い甲状腺未分化癌に対しては、唯一の承認薬であるレンバチニブもその効果が不十分なものであり、新規治療の開発が求められている。本研究の結果から、IRAK1/4InhibitorIがレンバチニブの効果を増強することが示された。その作用機序をより詳細に明らかにし、抗腫瘍効果および毒性の情報を蓄積することで、レンバチニブとIRAK1/4InhibitorIの併用療法が、甲状腺未分化癌に対する有望な治療法の開発につながるものと考えている。