Novel therapy for malignant peripheral nerve sheath tumors by extracellular matrix regulation

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16769
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nagoya University
• Principal Investigator: Ikuta Kunihiro 名古屋大学, 医学部附属病院, 病院講師 (40732657)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 肉腫 / 細胞外マトリックス / ヒアルロン酸合成阻害 / 悪性末梢神経鞘腫瘍

Outline of Final Research Achievements

The aim of this study is to elucidate the enhancement of the antitumor effects of chemotherapeutic agents by 4-MU in malignant peripheral nerve sheath tumors (MPNST). In vitro, we evaluated the proliferation, invasion, apoptosis, and hyaluronic acid concentration using human MPNST cell lines. When 4-MU was combined with chemotherapeutic agents approved for soft tissue sarcomas, some agents showed a reduction in the tumorigenicity of the cell lines compared to conditions where 4-MU or the chemotherapeutic agents were administered alone, and a decrease in the mRNA expression of membrane protein drug transporters was observed. Cell lines and PDX mouse models were created from MPNST patients. Validation in vivo remains a future task.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

MPNSTに有効な抗がん薬レジメンはない。新規薬剤の開発には膨大な時間とコストがかかるため、抗がん薬の分野では近年に上市される薬剤の単価は増加傾向にある。本研究で用いる抗がん薬は悪性軟部腫瘍に対して保険承認されており、4-MUは利胆剤として臨床で使用されていた。これらの併用療法が細胞外マトリックスの改変と薬剤輸送体の機能の抑制という側面から既存治療よりもMPNSTに対して抗腫瘍効果を示すことができれば、低コストで実践可能な治療法となりうる。