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A Model of a Zebrafish Avatar for Co-Clinical Trials
Alice Usai1, Gregorio Di Franco2, Patrizia Colucci1
1Department of Biology, University di Pisa, S.S. 12 Abetone e Brennero 4, 56127 Pisa, Italy.
Abstract:
Animal "avatars" and co-clinical trials are being developed for possible use in personalized medicine in oncology. In a co-clinical trial, the cancer cells of the patient's tumor are xenotransplanted into the animal avatar for drug efficacy studies, and the data collected in the animal trial are used to plan the best drug treatment in the patient trial. Zebrafish have recently been proposed for implementing avatar models, however the lack of a general criterion for the chemotherapy dose conversion from humans to fish is a limitation in terms of conducting co-clinical trials. Here, we validate a simple, reliant and cost-effective avatar model based on the use of zebrafish embryos. By crossing data from safety and efficacy studies, we found a basic formula for estimating the equivalent dose for use in co-clinical trials which we validated in a clinical study enrolling 24 adult patients with solid cancers (XenoZ, NCT03668418).
Insights
Researchers developed a cost-effective zebrafish embryo model for personalized oncology. They created a formula to convert human chemotherapy doses to fish, enabling better drug efficacy studies in co-clinical trials.
Area of Science:
- Oncology
- Translational Medicine
- Zebrafish Models
Background:
- Co-clinical trials and animal avatars are emerging tools for personalized cancer medicine.
- Zebrafish embryos offer a promising platform for avatar models due to their cost-effectiveness and rapid development.
- A key limitation in using zebrafish avatars is the lack of a standardized method for converting human chemotherapy doses to fish.
Purpose of the Study:
- To validate a simple, reliable, and cost-effective zebrafish embryo avatar model for oncology.
- To establish a formula for converting human chemotherapy doses to equivalent doses in zebrafish embryos for co-clinical trials.
- To validate the derived dose conversion formula in a clinical study involving adult patients with solid cancers.
Main Methods:
- Xenotransplantation of patient-derived tumor cells into zebrafish embryos to create avatar models.
- Conducting drug safety and efficacy studies in the zebrafish avatar models.
- Developing a formula for chemotherapy dose conversion from humans to zebrafish based on safety and efficacy data.
- Validating the dose conversion formula in a clinical trial (XenoZ, NCT03668418) with 24 adult cancer patients.
Main Results:
- A simple, reliable, and cost-effective zebrafish embryo avatar model was successfully validated.
- A basic formula for estimating equivalent chemotherapy doses for zebrafish avatars was derived from safety and efficacy data.
- The derived dose conversion formula demonstrated clinical relevance when validated in a patient cohort.
Conclusions:
- Zebrafish embryos provide a viable and cost-effective platform for developing avatar models in oncology.
- The established chemotherapy dose conversion formula facilitates the implementation of co-clinical trials using zebrafish avatars.
- This approach holds potential for advancing personalized medicine in cancer treatment by improving drug efficacy studies.
