Zebrafish Xenograft Model for Predicting Cisplatin Efficacy in Muscle-Invasive Bladder Cancer

Area of Science:

• Oncology
• Translational Medicine
• Zebrafish Xenografts

Background:

• Muscle-invasive bladder cancer (MIBC) standard treatment involves cisplatin (CDDP)-based neoadjuvant chemotherapy (NAC) and radical cystectomy.
• Limited patient response rates (approx. 40%) to NAC highlight the need for predictive tools.
• Zebrafish patient-derived xenograft (zPDX) models are cost-effective for drug testing but not yet established for MIBC.

Purpose of the Study:

• To develop and validate a zPDX model for assessing CDDP sensitivity in MIBC.
• To establish a clinically relevant platform for functional drug testing in bladder cancer.

Main Methods:

• Developed a zPDX model using clinical bladder cancer specimens.
• Validated the model through cell line-derived zPDXs, comparison with mouse PDXs (mPDX), and correlation with clinical outcomes.
• Utilized an image-based platform for quantifying drug response via fluorescent area measurement.

Main Results:

• Successfully established and validated the zPDX model for CDDP sensitivity evaluation.
• Demonstrated robustness through complementary assays including CAGE and immunofluorescence.
• Achieved successful prediction of CDDP efficacy using patient-derived tumors in zebrafish.

Conclusions:

• The zPDX model is a clinically relevant and experimentally validated tool for assessing CDDP sensitivity in bladder cancer.
• This platform shows potential for guiding personalized treatment decisions in MIBC.
• Further validation in larger cohorts is warranted to fully integrate this model into clinical practice.