Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients

The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generated by xenografting tumor tissues in two days post-fertilization zebrafish embryos. zPDXs were exposed to chemotherapy regimens (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) for 48 h. We used a linear mixed effect model to evaluate the zPDX-specific response to treatments showing for 4/36 zPDXs (11%), a statistically significant reduction of tumor size compared to controls. We used the RECIST criteria to compare the outcome of each patient after chemotherapy with the objective response of its own zPDX model. Of the 36 patients enrolled, 8 metastatic colorectal cancer (mCRC), response rate after first-line therapy, and the zPDX chemosensitivity profile were available. Of eight mCRC patients, five achieved a partial response and three had a stable disease. In 6/8 (75%) we registered a concordance between the response of the patient and the outcomes reported in the corresponding zPDX. Our results provide evidence that the zPDX model can reflect the outcome in mCRC patients, opening a new frontier to personalized medicine.

Automated summary

The use of zebrafish embryos (zPDX) has gained popularity in personalized medicine for predicting chemotherapy response in colorectal cancer patients. In this co-clinical trial, zPDXs exposed to different chemotherapy regimens exhibited significant reductions in tumor size compared to controls. The response of zPDXs correlated with the outcomes in a subset of metastatic colorectal cancer patients, indicating the potential for zPDX models in personalized medicine.