Zebrafish embryos as avatar of patients with pancreatic cancer: preliminary results of validation a new model toward personalized medicine

Purpose: The use of zebrafish as avatar for oncological patients toward personalized medicine is gaining popularity. The aim of this study is to develop a simple, not expensive and diffusible zebrafish embryo model as avatar for patients affected by pancreatic ductal adenocarcinoma (PDAC). Materials and methods: Tumor tissue, taken from the surgical specimen and fragmented into small pieces, was stained with CM-Dil and transferred in the yolk of zebrafish embryos. Embryos were incubated at 35°C in E3 medium in the presence or absence of the following drugs: Gemcitabine; Gemcitabine and Oxaliplatin; Gemcitabine and nab-Paclitaxel; 5-Fluorouracil and Folinic Acid and Oxaliplatin and Irinotecan. The response to the chemotherapy was analyzed by monitoring the fluorescent stained area at 2 hours, 1 day and 2 days’ post injection (dpi), normalizing it with respect to the 1 dpi time point (mean relative tumor area – mean RTA). We compared the mean RTA of each treated subgroup and the control group and analyzed the percentage reduction of the mean RTA trying to compare it to the partial response rate reported in clinical practice. Results: Between July 2018 and October 2019, 15 patients with PDAC were prospectively enrolled. A statistically significant reduction of the mean RTA in the treated subgroups for at least one chemotherapy scheme was reported in 6/15 (40%) cases. The analysis of percentage reduction of the RTA in treated subgroups revealed the presence of a linear relationship in each subgroup between the percentage reduction of the RTA and the number of cases reporting each percentage threshold considered for the analysis. Using the linear regression line equations, we calculated the expected RTA reduction corresponding to the percentage of partial response reported in the literature for each administered chemotherapy scheme. The mean conversion factor calculated was -60.4% for FOLFOXIRI, -59.3% for GEM-nab/P, -62.4% for GEMOX, and -63.7% for GEM (p=0.626). Conclusions: Zebrafish embryos could be a diffusible, not expensive model as avatar of patients with PDAC. We standardized the protocol for the xenotransplantation, for the exposition of the xenotransplanted zebrafish embryos to chemotherapy drugs, and for the evaluation of the efficacy of chemotherapy drugs