2022 Fiscal Year Final Research Report
Elucidation of metabolic mechanisms focusing on genomic abnormalities and epigenomic changes related to tumor-bearing state and drug resistance
| Project/Area Number |
19K07769
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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 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Yokohama City University (2022)
National Cancer Center Japan (2019) |
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Principal Investigator |
FUJII Satoshi 横浜市立大学, 医学研究科, 教授 (30314743)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | エピジェネティクス / メタボローム解析 |
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| Outline of Final Research Achievements |
The purpose of this study is to identify metabolites related to specific functions of cancer cells, and metabolites characteristic of genomic abnormalities and epigenomic changes. Then, we aim to detect cancer-bearing patients and elucidate the metabolite formation mechanism that can be a therapeutic target through metabolome analysis. The energy required for the survival and proliferation of cancer cells caused by genomic abnormalities and epigenetic changes is produced through metabolism, and metabolites are produced in the process of producing functional proteins related to cancer phenotype. 150 surgical specimens of head and neck squamous cell carcinomas originating in the four regions (oral cavity, larynx, oropharynx, hypopharynx) and plasma from 8 patients with esophageal squamous cell carcinoma and plasma from 8 non-cancer patients were used for the analysis of this study. Metabolites X and Y, which are involved in epigenetic regulation, were identified in this study.
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| Free Research Field |
エピジェネティクス
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| Academic Significance and Societal Importance of the Research Achievements |
頭頸部扁平上皮癌や食道扁平上皮癌には明確なドライバー遺伝子が見出されておらず、遺伝子異常に基づいた分子標的薬の開発が進んでいないがんのひとつである。メタボローム解析は、代謝経路の理解から、がんが生存するメカニズムを解明する有効な手段として注目されている。代謝経路とともにがんの生態を俯瞰的に理解することで、がんの新たな生物像を明らかにし、遺伝子異常のみに頼らない新しい治療法が期待される。我々の検討では、エピゲノム制御に関わる代謝物を見出していることから、代謝の変化とエピゲノム変化が連動し、その結果がんの形質が作られる可能性を指摘でき、新しい視点からのがんの生物像の理解と治療法の発展に寄与できる。
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