2021 Fiscal Year Final Research Report
Innovative histopathological diagnosis and therapy in osteosarcoma
| Project/Area Number |
19K07413
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
茶野 徳宏 滋賀医科大学, 医学部, 准教授 (40346028)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | RAB39A / RXRB / osteosarcoma / RDH10 / ovarian cancer / carbohydrate / cancer stem cell |
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| Outline of Final Research Achievements |
In osteosarcomas, RAB39A-RXRB pathway wasn't a clinicopathological biomarker. On the other hand, targeted RAB39A inhibition showed strong anticancer effects in many osteosarcomas, indicating that this molecular inhibition has broadly therapeutic applicability in osteosarcomas.
We further searched for molecules supporting RXRB-cancer stem pathway and identified RDH10, which is important for maintaining carbohydrate storage in ovarian cancer stem cells. Inhibiting RDH10-PEPCK-RXRB molecular pathway can reduce the cancer stem cell function in ovarian cancers, suggesting the molecular inhibition of this pathway will become a novel therapeutic target for ovarian cancers.
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| Free Research Field |
臨床病理学
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| Academic Significance and Societal Importance of the Research Achievements |
骨肉腫に於いてはRAB39A-RXRB経路は臨床病理学的なバイオマーカーとはなりませんでしたが、RXRBがん幹細胞経路を支援する分子探索を更に実施することで、RDH10分子を新規に同定しました。
RDH10分子は、骨肉腫ではなく、卵巣がんに於いて、がん幹細胞機能の維持に極めて重要であり、RDH10-PEPCK-RXRBの分子経路を阻害することで、卵巣がん幹細胞のcarbohydrate貯蔵能を抑制し、がん幹細胞機能を強く阻害できることが明らかになりました。本経路の阻害は、卵巣がんに対する新たな治療標的となり得ると考えられます。
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