Published online Jun 7, 2020. doi: 10.3748/wjg.v26.i21.2792
Peer-review started: December 31, 2019
First decision: February 24, 2020
Revised: March 27, 2020
Accepted: May 27, 2020
Article in press: May 27, 2020
Published online: June 7, 2020
The response of patients with pancreatic ductal adenocarcinoma (PDAC) to the different chemotherapy schemes is difficult to predict. The concept of precision medicine has emerged recently with the objective to tailor the medical treatment to the individual characteristics of each patient, and particularly to the tumor biology of each patient.
Recently, the use of zebrafish as avatar for oncological patients has gained popularity. However, only preliminary studies were conducted with patient-derived pancreatic cancer cells or tissue.
The aim of this study is to evaluate the usability of zebrafish embryos as a model possibly simple, not expensive and diffusible, that could be used as avatar for patients affected by PDAC, to predict the efficacy of the different chemotherapy schemes and the clinical response to the treatment.
A fragment of the tumor was taken from the surgical specimen and sectioned into about 3 mm3 pieces for DiI staining. Small pieces of stained tissue were xenotransplanted into the yolk of n = 100 zebrafish embryos 2 dpf. The zebrafish xenografts were incubated at 35°C with the presence or absence of drugs (GEM, GEMOX, GEM/nab-P, FOLFOXIRI) dissolved in fish water, using the equivalent dose (ED = 5). Firstly, we compared the mean relative tumor area (RTA) between each treated subgroup and the control group. Secondly, we evaluated the percentage reduction of the mean RTA (PRmRTA) in each treated subgroup in comparison to the control group, evaluating the presence of a linear relationship between each threshold value of the PRmRTA and the number of cases reporting a PRmRTA equal or greater to each threshold value. Using the linear regression line equation, we calculated for each protocol the expected percentage RTA reduction with the following formula: Expected percentage reduction of the mean RTA = (percentage of PR reported in literature – qlinear regression line equation)/mlinear regression line equation. For each chemotherapy protocol, we calculated the mean value of the expected PRmRTA and compared each other’s.
In the control group the Dil-stained areas showed a statistically significant increase over time in all cases, while a tendency to a reduction of the mean RTA was observed in treated subgroups, with a statistically significant reduction of the mean RTA for at least one chemotherapy scheme in 6/15 (40%) cases. The presence of a linear relation between the percentage reduction of the RTA and the number of cases reporting at least each percentage threshold was observed in each subgroup. The mean conversion factor was -60.4% for FOLFOXIRI, -59.3% for GEM-nab/P, -62.4% for GEMOX, and -63.7% for GEM (P = 0.626).
This study provides a simple, reliant and not expensive PDAC patients-derived xenograft model for the rapid pre-clinical evaluation of the efficacy of different chemotherapy schemes available for the treatment of each individual PDAC patient’s case.
Our model seems to reflect the clinical response rate reported in literature. However, to determinate the possible capability of our model in predicting the efficacy of the chemotherapy scheme administered to patients with PDAC, it is necessary to evaluate the correlation between these data and the real clinical response to adjuvant chemotherapy on patients. A co-clinical trial (NCT00070213) is underway in our institution and will be object of further publication.