2022 Fiscal Year Final Research Report
Development of a novel treatment for osteosarcoma with multi-kinase inhibitors
| Project/Area Number |
20K22802
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2020-09-11 – 2023-03-31
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| Keywords | 骨肉腫 / マルチキナーゼ阻害薬 / 患者由来組織移植モデル / 化学療法 |
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| Outline of Final Research Achievements |
The purpose of this study was to investigate the efficacy of multi-kinase inhibitors in osteosarcoma. To make the results relevant to clinical practice, a patient-derived orthotopic xenograft model, which has been reported to have high predictive ability in drug sensitivity test, was established using osteosarcoma patient tissues. Two osteosarcoma patient-derived orthotopic xenograft models were treated with the clinically available multi-kinase inhibitors pazopanib, sorafenib, sunitinib, regorafenib, crizotinib, and the first-line drug cisplatin. Mild growth inhibition in the sunitinib and sorafenib groups and marked growth inhibition with tumor regression in the regorafenib group were observed. In the regorafenib group, pathologic sections showed complete necrosis of the tumor. We believe that regorafenib is effective in osteosarcoma.
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| Free Research Field |
整形外科
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| Academic Significance and Societal Importance of the Research Achievements |
患者由来組織同所移植モデルによる解析は，研究結果が臨床に直結しやすく，見出した薬剤をドラッグリポジショニングすることで，新規の治療薬として臨床応用に繋げることが期待できる．骨肉腫は希少がんである故に，治療法の進歩が少ないため，他の癌腫に比べ，使用できる薬剤が少なく，治療成績も30年以上にわたり変化していない．マルチキナーゼ阻害薬も他癌腫では広く用いられており、骨肉腫に有用な可能性を指摘されているが、臨床応用されていない．本研究の解析結果でレゴラフェニブが骨肉腫に有用な可能性を見出すことができ，骨肉腫治療対する新しい治療戦略の開発に寄与すると確信している．
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