2021 Fiscal Year Final Research Report
Established epigenetic treatment for chemotherapy-resistant metastatic bladder cancer
| Project/Area Number |
19K09706
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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 56030:Urology-related
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| Research Institution | University of Toyama |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
金井 弥栄 慶應義塾大学, 医学部(信濃町), 教授 (00260315)
北村 寛 富山大学, 学術研究部医学系, 教授 (00404674)
鈴木 拓 札幌医科大学, 医学部, 教授 (20381254)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 膀胱癌 / エピジェネティクス / 5-Aza-CdR / 2次治療 |
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| Outline of Final Research Achievements |
Chromatin accessibility was analyzed by the AcceSssIble assay, revealing that the CDDP / GEM-resistant cell lines differ in histone-modified regions compared to the parental strain. It was clarified that the change in chromatin structure due to histone modification contributed to the drug resistance. Comprehensive DNA methylation analysis revealed that resistance was not contributed by genetic changes at a particular site, but by both genome-wide DNA methylation changes and structural changes due to histone modifications. In an in vivo study, low-dose 5-aza-CdR showed a synergistic effect with CDDP administration, and a growth-suppressing effect was also observed in resistant strains.
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| Free Research Field |
膀胱癌
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| Academic Significance and Societal Importance of the Research Achievements |
化学療法抵抗性と5-Aza-CdRによる化学療法再感受性のメカニズム解明を明らかにしたことで、今後5-aza-CdRのGC療法の2次治療としての臨床試験の応用の可能性がついた。予後不良である転移性膀胱癌に対して5-Aza-CdRを組み合わせた2次治療が臨床応用されることで、新たな治療法の開発につながり、多くの膀胱癌患者の予後延長効果が期待される。
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