2022 Fiscal Year Final Research Report
Elucidation of molecular mechanisms and development of novel therapeutic agents in pulmonary metastasis of osteosarcoma
| Project/Area Number |
19K16760
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Chiba Cancer Center (Research Institute) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 骨肉腫 / レドックス / チオレドキシン (TXN) / PX-12 / TXN還元酵素 (TXNRD) / オーラノフィン (AUR) / 患者腫瘍組織移植モデル(PDX) |
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| Outline of Final Research Achievements |
Osteosarcoma has a poor prognosis due to local progression and pulmonary metastasis, both of which must be controlled. In the current study, we focused on thioredoxin and thioredoxin reductase inhibitors, PX-12 and auranofin (AUR), to elucidate the involvement of oxidative and reductive (redox) regulation in osteosarcoma, respectively. PX-12 inhibited local progression and AUR also inhibited pulmonary metastasis. The combination of celecoxib and AUR was also examined to determine synergistic effects with other oxidative stress-inducing agents. The combination of celecoxib and AUR synergistically suppressed local progression of osteosarcoma. Patient-derived xenografts (PDX) models of osteosarcoma and chondrosarcoma were successfully generated and will be applied in future studies.
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| Free Research Field |
骨・軟部肉腫
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| Academic Significance and Societal Importance of the Research Achievements |
骨・軟部肉腫ではレドックス制御の報告は限られており，本研究のさらなる発展によりレドックス関連阻害剤の骨・軟部肉腫への応用が期待できる．また，AURはすでに本邦において承認されており，抗リウマチ薬としても用いられている安全性の高い内服薬である．近年，ドラッグリポジショニングが注目されており，今後AURの骨肉腫への効果がPDX等でも証明できれば，AURの臨床応用も早期可能であると考えられる．またPDXはヒトの病態に最も近いモデルであり，現在骨肉腫も含めた様々な骨・軟部肉腫のPDX作成を継続しており，今後のレドックス制御の解明を含め様々な研究の基盤になると考える．
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