Analysing cellular characterizationAnalysis of treatment resistance mechanisms in lung metastasis of bone and soft tissue sarcomas

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: 医療法人徳洲会野崎徳洲会病院(附属研究所)
• Principal Investigator: Sasagawa Satoru 医療法人徳洲会野崎徳洲会病院(附属研究所), 研究所, 主任研究員 (80345115)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 滑膜肉腫 / Twist1 / MICA/B / スフェロイド / HDAC阻害剤

Outline of Final Research Achievements

There are a few drugs available for synovial sarcoma treatment, and increasing drug choices is an urgent issue in clinical practice. In this study, I focused on an HDAC inhibitor, romidepsin, and showed that the expression of MICA/B, which is recognized by NK cells, can be induced with low-dose romidepsin treatment. We found that synovial sarcoma cells display strong drug resistance under 3D culture (spheroid form) conditions, which was caused by the Twist1 molecule. I also showed that the drug SN38 could release drug resistance by suppressing the expression of Twist1. These results could be the cornerstone of novel drug therapies for synovial sarcoma and pathways to avoid drug resistance.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

滑膜肉腫に対する新規薬剤の開発および薬剤耐性メカニズムの解明は臨床現場から強く希求される課題である。本研究ではHDAC阻害剤の新規利用法としてMICA/Bの誘導による自己の免疫による治療アプローチの可能性および、3次元形態で顕在化する薬剤耐性メカニズムを解明した。滑膜肉腫の治療薬としてのHDAC阻害剤の阻害剤の重要性を示したことに加えて、抗がん剤開発基礎研究における標準的な2次元培養に潜むリスクと3次元培養が抗がん剤研究における有効性を持つことを示した点で、その研究波及効果は大きいと考えられる。