In vivo toxicity assays in zebrafish embryos: a pre-requisite for xenograft preclinical studies

Area of Science:

• Oncology
• Toxicology
• Zebrafish Models

Background:

• Human cancer cell xenografts in zebrafish embryos are valuable preclinical oncology tools.
• Limited studies have addressed the host toxicity limits of anticancer drugs in this model.

Purpose of the Study:

• To evaluate the acute toxicity of five common human anticancer drugs in zebrafish embryos.
• To compare toxicity data from *in vitro* assays and zebrafish embryo tests at different developmental stages.
• To determine the reliability of toxicity data for xenograft studies.

Main Methods:

• Five anticancer drugs (Carboplatin, Irinotecan, Doxorubicin, Paclitaxel, Chloroquine) were tested.
• Fish Embryo Acute Toxicity (FET) tests were conducted on zebrafish embryos at 0 and 72 hours post-fertilization (hpf).
• Results were compared with *in vitro* toxicity assays.

Main Results:

• Significant differences in toxicity were observed between *in vitro* and *in vivo* zebrafish embryo models.
• Toxicity data from *in vitro* assays and FET tests at 0 hpf did not reliably predict xenograft outcomes.
• FET tests at 72 hpf provided more relevant toxicity information for xenograft studies.

Conclusions:

• Toxicity evaluation at 0 hpf in zebrafish embryos is insufficient for predicting drug safety in xenograft models.
• Additional toxicity studies using 72 hpf zebrafish embryos are necessary for reliable preclinical oncology research.
• Optimizing toxicity assessments in zebrafish models is crucial for advancing cancer drug development.