Zebrafish is a very versatile model to analyze the function of specific cancer-related genes via different approaches, such as modulation of gene expression, gene knockout, generation of transgenic lines and tumor cells transplantations. Moreover, tumors show a relevant degree of histological similarity compared to those present in humans. This explains how, in the past years, the zebrafish has become one of the most powerful preclinical models for mimicking different human diseases, in particular, tumors onset and spreading. This review highlights the importance of the zebrafish model for cancer research, in particular providing insights into the state of art of this teleost as a model for the study of melanoma biology.

Despite the differences between zebrafish and human epidermis, the melanomas affecting both species are very similar. In addition, humans and zebrafish share the developmental program that specifies for the formation of melanocytes. It was shown that, in zebrafish, the genetic regulation of melanocytes specification relies upon the nacre/mitfa gene, direct target of the Wnt signaling; moreover, the serine/threonine kinase BRAF is involved in nevi formation such that human BRAF mutations were found to be associated with melanoma development both in humans and fish. A more recent work has shown how the zebrafish can be exploited to follow melanoma development in vivo from its onset as a single cell, demonstrating that tumor occurrence is accompanied by the reemergence of a neural crest progenitor state in the cells that will originate the malignancies.

Further exploitation of the zebrafish melanoma model will be instrumental for a better understanding of this disease and for developing focused therapeutic strategies.