Zebrafish embryo as avatar of oncological patients: preliminary experience toward a personalized medicine

The aim of this study is to evaluate the usability of Zebrafish embryos (ZE) as avatar of patients affected by colorectal (CR) cancer, colorectal liver metastasis (CRLM) or pancreatic cancer. Methods: For each enrolled patient, a fragment of the tumor was xenotransplanted inside the yolk of 2 day post-fertilization ZE. Two hours post-injection (hpi) transplanted ZE were incubated in only E3 media (control-ZE group) or with added standard combinations of chemotherapy (treated-ZE subgroups) for 48 hours. A ratio between the tumor mass area at 24 hpi and 48 hpi and the percentages of cell migration through the ZE caudal vein were calculated in the both groups and compared to each other. Results: Six patients with pancreatic cancer (PC-group), ten patients with colon cancer (CR-group) and two patients with colorectal liver metastasis (CRLM-group) were enrolled between January 2018 and November 2018. In all cases of the control-ZE group the tumor mass increased at 48 hpi respect 24 hpi. A statistically significant difference of tumor mass progression in the treated-ZE subgroups respect the control-ZE subgroup was observed in 3/6 cases (50%) in PC-group, in 4/10 cases (40%) of CR-group and 2/2 (100%) cases of CRLM-group. Cell migration was detected in ZE of the control-ZE group in 3/6 cases (50%) in PC-group, 7/10 cases (70%) in CR-group, 2/2 cases (100%) of CRLM-group. A significant reduction of the cell migration in the treated-ZE subgroups was revealed for almost one chemotherapy scheme in all cases in all groups. Conclusions: In our experience, zebrafish embryos could be a used as avatar for oncological patients because in all cases the tumor cells successfully grafted in the yolk sack of zebrafish embryos. A prospective co-clinical trial is under way to evaluate the concordance between the results of tests in ZE and the response to chemotherapy in oncological patients.