| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| 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.
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