2023 Fiscal Year Final Research Report
Investigation of the molecular mechanism mediating the resistance to combined treatment with IO drug and TKI in renal cell carcinoma and the development of the novel therapy targeting this mechanism
| Project/Area Number |
21K09341
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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 | Kobe University (2023)
Hamamatsu University School of Medicine (2021-2022) |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 腎細胞癌 / チロシンキナーゼ阻害剤 / IO drug / 治療抵抗性 |
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| Outline of Final Research Achievements |
Several assessments were performed using a model system using mouse renal cell carcinoma cell line, RenCa, acquired resistance to IO-TKI combination therapy, and we identified a few candidate genes involved in the acquired resistance to IO-TKI combination therapy. We then generated antisense oligonucleotide targeted against these genes, and confirmed the inhibitory effects on the expression of these genes. We currently examine whether the acquired resistance to IO-TKI combination therapy could be overcome by the additional treatment with antisense oligonucleotide. In addition, we analyzed the mechanism involved in the enhanced antitumor activity by additional treatment with antisense oligonucleotide.
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| Free Research Field |
泌尿器科
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| Academic Significance and Societal Importance of the Research Achievements |
腎細胞癌は高頻度に遠隔転移を来し、抗癌剤および放射線療法に高度の耐性を有することで知られている。今後の進行腎細胞癌治療に対して中心的役割を果たしていくと考えられるIO-TKI併用療法に対する治療抵抗性機序が明らかになれば、同療法に抵抗性となる期間を延長し得る有用な新規併用療法の確立に繋がる可能性があると考えられ、転移性腎細胞癌患者の予後改善を目指した多角的な新規治療戦略構築へ向けて大きな成果が得られるものと期待される。
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