2023 Fiscal Year Final Research Report
Development of molecular-targeted therapeutic drugs for malignant glioma that enable reactivation of tumor immunity
| Project/Area Number |
20K09333
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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 56010:Neurosurgery-related
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| Research Institution | Hokuriku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井上 明宏 愛媛大学, 医学部附属病院, 講師 (20593403)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | グリオーマ / 腫瘍幹細胞 / 腫瘍免疫 / Oct-3/4 |
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| Outline of Final Research Achievements |
This research aims to find a compound that suppresses Oct-3/4 expression and also suppresses anti-tumor immunity. The 24 candidate compounds have been obtained from a library of 640 compounds. When a secondary screening was performed, Compound F was obtained which had low cytotoxicity and exhibited a significant cell proliferation inhibitory effect. On the other hand, compound F did not inhibit cell proliferation of normal astrocytes. Therefore, when compound F was administered to a mouse glioma model, shrinkage of the formed glioma was observed. Docking simulation analysis has revealed that Compound F is an activator that binds to AMPK, and we would like to investigate a detailed study in the future.
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| Free Research Field |
病態生理学
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| Academic Significance and Societal Importance of the Research Achievements |
グリオーマ治療においても免疫細胞の再活性化による腫瘍免疫治療薬が手術、放射線治療、化学療法に次ぐ「第4の柱」になりうるとして、国内外で研究開発が進められている。しかしながら、臨床試験段階ではあるものの有効性が報告されたものは少ない。
本研究結果は、免疫の中心的な役割を果たすT細胞の機能をOct-3/4が抑制し、グリオーマ細胞が宿主免疫システムから回避して増殖している可能性を示唆するものである。したがって、化合物Fは、Oct-3/4を抑制することで、浸潤、腫瘍幹細胞、腫瘍血管新生、薬剤耐性に加え、抗腫瘍免疫をも標的とし、停滞するグリオーマ治療の突破口になる可能性が期待される。
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