Cancer cell xenografts in zebrafish embryos as an experimental tool in drug screening for adrenocortical carcinoma

Despite the widespread use of murine models in in-vivo experiments, the zebrafish (Danio rerio) offers unique advantages that make it a versatile and faster preclinical model for drug screening, particularly for adrenocortical carcinoma (ACC), a rare malignancy with limited preclinical models that reflect patient heterogeneities. Over the past decade, significant progress has been made with models like cell lines, organoids, and murine models, which are crucial for advancing disease understanding and treatment development. However, recent reviews have overlooked zebrafish model for ACC. This mini review aims to fill this gap by detailing the advancements of the zebrafish model in ACC research. Recent studies have utilized zebrafish embryos xenografted with ACC cells as a novel approach to studying drug effects on tumor growth and metastasis, consistent with studies regarding other tumors. Specifically, it was demonstrated the ability of abiraterone acetate, trabectedin and progesterone to significantly reduce the tumor area at non-toxic-concentrations. Interestingly, this model allowed to confirm in vivo that metastasis-derived cells were able to metastasize and that trabectedin and progesterone reduced the rate of embryos with metastasis. One more study showed that metastasis formation was significantly reduced in H295R/TR-SF-1-xenografted embryos after fascin1 knock-out or inhibition with G2-044. Even with some limitations, the zebrafish xenografts offer a suitable and expeditious animal model for the screening of potentially effective drugs, identification of dose toxicity, and determination of the most promising compounds for more advanced preclinical phases, especially in rare diseases with limited therapeutic options such as ACC.