Cancer is a genetically complex disease that results from the multistep accumulation of somatic, and occasionally inherited, mutations that result in clonal neoplastic cell transformation. Mouse models have provided important insights into these collaborating genetic events that cause cancer formation. Nevertheless, invertebrate models are generally unable to recapitulate the pathogenesis of many human diseases. Due to its small size, rapid maturation time, and heavy brood, the zebrafish has emerged as an important new cancer model. Advances in transgenic and mutagenesis strategies have already resulted in a wide variety of zebrafish cancer models with distinct capabilities for high-throughput screening and in vivo imaging. Besides, the establishment of transgenic lines expressing fluorochromes, such as green fluorescent protein (GFP), in specific developing tissues makes the transparent developing zebrafish particularly conformable to in vivo studies of neoplastic progression, metastasis, and remission.
There are some long-standing methods for establishing a cancer model in zebrafish, including carcinogenic treatment, transgenic regulation, and the transplantation of mammalian tumor cells. By inducing different gene mutations or activating signaling pathways through the use of chemicals, tumors can be induced in multiple organs in zebrafish, such as the liver, pancreas, intestinal canal, muscle, skin, vasculature, and testis. Transgenic technology allows the formation of specific types of tumor by the overexpression of particular oncogenes. All these reverse genetic approaches aim to create a loss-of-function phenotype or they aim to transfer genes found mutated in human cancer patients into the fish. This could also mean generating a zebrafish model with a mutation in an orthologous gene to a human cancer-related phenotype. The xenotransplantation of mammalian tumor cells into zebrafish provides a novel method of studying the interactions between the transplanted tumor cells and the host's vasculature.
Creative Biogene has established more than 50 genetically engineered zebrafish models of human cancer that closely resemble their human counterparts at the histological and/or genomic levels. Our zebrafish cancer models have accelerated the discovery of new mechanisms driving human cancers and identified new drugs for clinical trials. By using a combination of chemical treatment, genetic technology, and tumor cell xenotransplantation, the vast majority of human tumors can be modeled in zebrafish.