Zebrafish Xenograft Model for Cisplatin Efficacy in Human Bladder Cancer
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard treatment for muscle-invasive bladder cancer (MIBC); however, the NAC response rate is 40% and we lack predictive biomarkers. Patient-derived xenograft (PDX) models are promising avenues for drug evaluation; however, establishing mouse PDX (mPDX) models is time-consuming, especially for MIBC patients who require treatment soon. Zebrafish offers a rapid and cost-effective alternative, although zebrafish PDX (zPDX) models for bladder cancer are rare. We developed a zPDX model to predict cisplatin (CDDP) efficacy in MIBC using a 3-step approach. Fluorescently labeled bladder cancer cell lines (CDDP-sensitive and CDDP-resistant) were transplanted into zebrafish embryos to establish an imaging-based efficacy evaluation system. We then compared CDDP responses between the mPDXs and the corresponding zPDXs. Finally, bladder cancer tissues resected transurethrally from patients were transplanted into zebrafish, and CDDP efficacy in zPDXs was compared with NAC outcomes in the same patients. In all steps, bladder cancer cells rapidly engrafted into zebrafish, enabling evaluation of CDDP efficacy. The results of zPDX models were consistent with the expected effects of CDDP observed in in vitro studies, mPDX models, and clinical patients. The zPDX is a rapid and promising avatar model for guiding personalized treatment in MIBC.