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).
Highlights
Precision medicine refers to the tailoring of medical treatment to the individual characteristics of each patient [1]
A dose-response analysis to determine the effects of chemotherapy treatment on embryos was based on an evaluation of the phenotype resulting from the exposure
For the multidrug combination chemotherapy (Tables S1 and S2), we mixed drugs at the mass ratio used for humans, i.e., Gemcitabine + Oxaliplatin (GEMOX) was 10:1 in Gemcitabine:Oxaliplatin; GEM/nab-P was 8:1 in Gemcitabine:nab-Paclitaxel; Gemcitabine + Cisplatin (GEMCIS) was 40:1 in Gemcitabine:Cisplatin; Fluorouracil + Lederfolin + Oxaliplatin (FOLFOX) was 33:2.4:1 in
Summary
Precision medicine refers to the tailoring of medical treatment to the individual characteristics of each patient [1]. The “mouse avatar” is an emerging approach in precision medicine in oncology which has recently increased in importance [2] It involves the xenotransplantation of cancer cells from the patient’s tumor sample into mouse models for use in drug efficacy studies. In a co-clinical trial, the patient and murine trials are conducted simultaneously, and the drug efficacy response of the mouse study provides data to plan the best drug treatment for the patient’s tumor [4]. The advantage of this approach is that each patient has his/her own tumor growing in an in vivo system, thereby facilitating the development of a personalized therapeutic approach. This means that avatars are a cutting-edge technology that few can afford, posing a serious threat to the equal right to health for everyone
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