2021 Fiscal Year Final Research Report
The combination therapy of immuno-checkpoint inhibitor with anti NOTCH2 antibody for chemotherapy resistant bladder cancer
| Project/Area Number |
19K09729
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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 | Hiroshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松原 昭郎 広島大学, 医系科学研究科(医), 教授 (10239064)
亭島 淳 広島大学, 医系科学研究科(医), 准教授 (20397962)
安井 弥 広島大学, 医系科学研究科(医), 名誉教授 (40191118)
井上 省吾 広島大学, 病院(医), 講師 (90457177)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 薬剤耐性膀胱がん / PD-1抗体 / NOTCH2/HEY1シグナル |
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| Outline of Final Research Achievements |
Using gemcitabine- and cisplatin-resistant bladder cancer cell lines and their parental lines, in vitro evaluation of cell proliferation and invasiveness with anti-NOTCH2 antibodies and public databases such as TCGA have revealed that NOTCH2/HEY1 signaling is involved in bladder cancer progression. The results of this study are summarized in the following table. In clinical specimens resistant to anticancer drugs, STAT1 signaling was upregulated, correlating with increased PD-L1 expression and lymphocyte infiltration. We expect that the combination of molecular targeted therapy in addition to immune checkpoint inhibitors will improve therapeutic efficacy in drug-resistant bladder cancer.
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| Free Research Field |
膀胱癌
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| Academic Significance and Societal Importance of the Research Achievements |
TCGAなどのpublic databaseと 臨床検体、細胞株によるin vitroのデータを統合することで、コホートによるバイアスを減らし、より正確に研究を遂行できることを研究を通じて実感した。薬剤耐性の膀胱癌に免疫チェックポイント阻害剤に加え分子標的治療を併用することの意義を臨床試験で明らかにされることを期待している。
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