Effectiveness of a novel tyrosin kinase inhibitor in Ewing sarcoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19656
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: University of Miyazaki
• Principal Investigator: Sawa Daisuke 宮崎大学, 医学部, 助教 (10632721)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ユーイング肉腫 / TAE226 / FAK / IGFIR / 細胞内シグナル

Outline of Final Research Achievements

High focal adhesion kinase (FAK) transcript expression levels in EWS cell lines are known. TAE226 is a dual inhibitor of FAK and insulin-like growth factor-I receptor (IGF-IR), while PF-562,271 is a dual inhibitor of FAK and proline-rich tyrosine kinase 2. We compared the cytotoxicity of TAE226 and PF-562,271 toward three EWS cell lines. Furthermore, we investigated the efficacy of TAE226 as well as its mechanism of action against EWS. TAE226 strongly inhibited proliferation of three cell lines when compared with PF-562,271. TAE226 strongly inhibited proliferation of three cell lines when compared with PF-562,271. TAE226 treatment of EWS cell lines induced cell cycle arrest, apoptosis, AKT dephosphorylation, and inhibition of invasion. We demonstrated that TAE226 drastically inhibits the local growth of primary tumors and metastasis in EWS using mouse models. Furthermore, the combination of TAE226 and conventional chemotherapy proved to exert synergistic effects.

Free Research Field

血液腫瘍学、小児科学

Academic Significance and Societal Importance of the Research Achievements

再発および転移性ユーイング肉腫の予後は、非常に不良である。
従って、腫瘍特異性のターゲットを特定し治療を行うことは、予後を改善させるために重要である。今回、評価をおこなったTAE226は、単剤あるいは既存の化学療法薬との併用により再発/転移性ユーイング肉腫の予後を改善させる可能性がある。