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- 2025/10/31
- Zebrafish Xenograft Model for Predicting Cisplatin Efficacy in Muscle-Invasive Bladder Cancer
| 2025/10/31 |
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Zebrafish Xenograft Model for Predicting Cisplatin Efficacy in Muscle-Invasive Bladder Cancer
Yusuke Sugino, Xin Bao, Sho Sekito, Shiori Miyachi, Takumi Kageyama, Takeshi Sasaki, Kouhei Nishikawa, Toshio Tanaka, Manabu Kato, Yasuhito Shimada, Keishi Takano, Raku Son, Liqing Zang, Kenji Nakayama, Masatoshi Watanabe, Yasuhiro Murakawa, Takahiro Inoue
Cancer Sci. 2025 Oct 8.doi: 10.1111/cas.70217.
ABSTRACT
The standard treatment for muscle-invasive bladder cancer (MIBC) is cisplatin (CDDP)-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy. However, only about 40% of patients respond to NAC, and tools to predict individual responses remain limited. The zebrafish patient-derived xenograft (zPDX) model offers a rapid and cost-effective platform for functional drug testing, but its application to MIBC has not yet been established. In this study, we developed a zPDX model optimized for evaluating CDDP sensitivity using clinical bladder cancer specimens. This model was validated through three steps: (1) evalu-ation of CDDP response in zPDXs derived from cell lines, (2) comparison of drug responses between mouse PDX (mPDX) and zPDX models, and (3) correlation of zPDX responses with clinical outcomes. The robustness of step 1 was demonstrated through complementary assays, including temperature optimization, in vivo platinum quantification, fluorescent dye validation, Cap Analysis of Gene Expression (CAGE), and whole-mount immunofluorescence. An image-based platform for quantifying drug response by measuring fluorescent area was established and applied in steps 2 and 3. Step 2, using mPDXs, provided essential technical validation before applying the protocol to clinical samples. In step 3, patient-derived tumors were transplanted into zebrafish, allowing successful prediction of CDDP efficacy. Despite the small patient cohort, this study provides fundamental ev-idence supporting zPDX as a clinically relevant and experimentally validated tool for functional assessment of CDDP sensitivity in bladder cancer.
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