Individualized molecular targeted therapy and biomarker discovery for malignant bone and soft tissue tumors

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18481
• 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 (2021-2022); Osaka International Cancer Institute (2019-2020)
• Principal Investigator: Imura Yoshinori 大阪大学, 大学院医学系研究科, 助教 (40772687)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 悪性骨軟部腫瘍 / 分子標的治療 / バイオマーカー / 容体型チロシンキナーゼ / 骨肉腫 / CIC-DUX4肉腫 / 淡明細胞肉腫

Outline of Final Research Achievements

The activation of PDGFRα, AXL, and FLT-3 was detected in highly metastatic mouse OS cell line LM8 and several human OS cell lines. The novel multiple RTK inhibitor TAS-115 suppressed the proliferation and survival of these OS cell lines by blocking PDGFRα, AXL, and FLT-3 phosphorylation both in vitro and in vivo. We suggest that TAS-115 be a promising therapeutic option for patients with metastatic or relapsed OS. We successfully established a novel human CIC-DUX4 sarcoma cell line designated Kitra-SRS. Treatment with the IGF-1R inhibitor attenuated Kitra-SRS cell growth and inhibited autocrine activation of IGF-1/IGF-1R and its downstream signalling pathways both in vitro and in vivo.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

公的な細胞バンクから入手可能な骨軟部肉腫細胞株のみならず、我々が肉腫患者の臨床検体から樹立した肉腫細胞株を用いて、生存や増殖に影響を与える受容体型チロシンキナーゼと下流シグナル活性化のメカニズムを解明し、治療効果の期待できる分子標的治療を考案した。組織型が多彩で発生頻度が稀であるが故に臨床試験が実施しにくい骨軟部肉腫領域において、本研究が肉腫に対する新規分子標的治療の開発に繋がるエビデンス構築に大きく貢献する。