Investigation of Wnt-signaling-targeted therapy for osteosarcoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15249
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Keio University
• Principal Investigator: Hirozane Toru 慶應義塾大学, 医学部(信濃町), 助教 (70594539)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 骨肉腫 / Wntシグナル / がん幹細胞性 / 分化転換

Outline of Final Research Achievements

The purpose of this study was to clarify the mechanism of action and efficacy of Wnt-signal-TNIK-targeted therapy for osteosarcoma, and to apply the results to clinical practice. We focused on TNIK, which positively regulates Wnt signaling, to study the treatment of osteosarcoma by targeting Wnt signaling. The results of this study suggested that TNIK could be a potential therapeutic target for osteosarcoma and suggested new mechanisms of action, such as loss of cancer stemness and induction of conversion to adipocytes with metabolic changes. We plan to further investigate companion markers of TNIK inhibitors for clinical application.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

骨肉腫に対する薬物治療としては，20-30年来，細胞障害性の抗がん剤を主体とした治療法が中心であり，有効な分子標的が見つかっていない．本研究から骨肉腫に対し，Wntシグナル・TNIKを標的とした治療法の有効性が示唆された．