2023 Fiscal Year Final Research Report

Clinical application of patient-derived xenograft zebrafish model of bladder cancer for evaluating drug efficacy and discovering new seeds of treatment

Research Project

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Project/Area Number	21H03066
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 56030:Urology-related
Research Institution	Mie University
Principal Investigator	INOUE TAKAHIRO 三重大学, 医学系研究科, 教授 (80511881)
Co-Investigator(Kenkyū-buntansha)	田中利男三重大学, 医学系研究科, 特定教授 (00135443) 佐々木豪三重大学, 医学部附属病院, 講師 (20644941) 内田克典三重大学, 医学部附属病院, 講師 (60362349) 加藤学三重大学, 医学部附属病院, 助教 (60626117)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	膀胱癌 / ゼブラフィッシュ / 異種移植モデル / シスプラチン
Outline of Final Research Achievements	We have developed human bladder cancer zebrafish xenograft model, which can predict cisplatin sensitivity, by implanting three type of bladder cancer cells: 1) Cisplatin-sensitive bladder cancer cell line, UMUC3 and T24, 2) bladder cancer cells derived from newly established human bladder cancer mouse xenograft models (MieUC series), 3) human bladder cancer tissues directed collected by transurethral resection. This patient-derived xenograft model would be applied to muscle invasive bladder cancer patients for selecting appropriate candidates of cisplatin-based neoadjuvant chemotherapy before radical cystectomy. Moreover, it could also be used to select appropriate drugs for treating patients using their own cancer tissues and realize personalized medicine in the future.
Free Research Field	泌尿器腫瘍学
Academic Significance and Societal Importance of the Research Achievements	転移のない筋層浸潤性膀胱癌患者はCDDPを含む化学療法(NAC)を膀胱全摘除術前に行うことが標準的治療であるが、効果は40%と限定であり、効果のない患者はこのNACによる治療の遅れが問題である。従って、NACの効果を予測するマーカーや検査方法の開発が望まれるが、臨床応用可能な方法はない。本研究成果をもとにゼブラフィッシュ異種移植モデルを用いた薬効評価系が確立されれば、この薬剤効果予測に基づいた個別化医療への応用が可能と考える。