High-throughput screening of soft tissue sarcoma cell lines for new drug development

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18498
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Osaka University
• Principal Investigator: Otani Hidetatsu 大阪大学, 医学系研究科, 講師 (60727965)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 軟部肉腫 / エピゲノム

Outline of Final Research Achievements

Soft tissue sarcomas (STSs) are malignant tumors that originate from mesenchymal tissues such as muscle, fat, and nerve. STSs consist of more than 50 subtypes. The aim of this study is to developing new anti-tumor drugs for STSs using high-throughput screening. We identified agent A as anti-tumor drug for clear cell sarcoma, which is one of a rare subtype of STSs harboring tumor specific fusion oncogene EWS-ATF1. We also found that agent A suppresses the expression of EWS-ATF1 that resulted in tumor growth suppression. Unfortunately, we failed to find new anti-tumor compounds against STSs among natural extracts that are preserved as Osaka University natural extracts libraries.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

我々は希少癌である軟部肉腫の1亜型である淡明細胞肉腫に効果が期待できる薬剤をハイスループットスクリーニングを行い同定しました。またその作用機序の一端として本腫瘍特異的な癌遺伝子であるEWS-ATF1の発現を抑制することが確認できました。明細胞肉腫は抗がん剤の感受性が乏しく治療選択肢の少ない組織型であるため今回同定した薬剤についてさらに詳しく研究を行い、EWS-ATF1発現制御のメカニズムなど薬剤の作用機序を解明することにより淡明細胞肉腫に対する治療選択肢の幅を広げることが期待できます。