Abstract
Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New therapeutic strategies are therefore urgently needed. The use of animal models represents a relevant tool for preclinical screening of new molecules/strategies against HCC. However, several issues, including animal husbandry, limit the use of current models (rodent/pig). One animal model that has attracted the attention of the scientific community in the last 15 years is the zebrafish. This freshwater fish has several attractive features, such as short reproductive time, limited space and cost requirements for husbandry, body transparency and the fact that embryos do not show immune response to transplanted cells. To date, two different types of zebrafish models for HCC have been developed: the transgenic zebrafish and the zebrafish xenograft models. Since transgenic zebrafish models for HCC have been described elsewhere, in this review, we focus on the description of zebrafish xenograft models that have been used in the last five years to test new molecules/strategies against HCC.
Highlights
While transgenic tumor models of hepatocellular carcinoma (HCC) have already been reported [4], here we focus on the description of the zebrafish xenograft model of HCC
We developed an HCC zebrafish xenograft model based on the use of JHH6 [44]
Chronic hepatitis B/C virus infection, alcohol abuse and nonalcoholic fatty liver disease are major causes of liver fibrosis (LF), which inevitably leads to progressive impairment of liver function, often culminating in HCC
Summary
It is evident that further improvement in the understanding of the disease and identification of new therapeutic molecules/strategies are urgently needed. In this regard, the use of animal models represents a relevant tool. The husbandry of these animals is not free of limitations, and rodent models do not necessarily reflect the pathophysiology of human cancers. The cost and husbandry requirements of this animal model make it unsuitable for large-scale drug screening. We focus on the papers published in the last five years that use the zebrafish to develop new strategies against HCC; the advantages and disadvantages of the described approaches are highlighted. Before presenting the experimental work performed, some details about HCC and the general characteristics of the zebrafish model are described
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