Zebrafish as a Xenotransplantation Model for Studying Cancer Biology and Cancer Drug Discovery

Abstract

AbstractVarious malignancies have been successfully recapitulated in mammalian animal models, where mimicking the systemic and local environment of the developing tumor has contributed to our understanding related to the mechanisms of cancer, their diagnosis and possible therapeutic interventions to contain the growth and survival of the cancer. Advances in research have facilitated generation of these animal models of cancer by application of sophisticated technologies with integration of clinical information. Until now, rodent models especially mouse models have been the traditional models of choice for cancer investigation. Over the last decade, Danio rerio, commonly known as zebrafish, has emerged as a popular model to study many human disorders including cancer. Zebrafish offers several advantages over rodent models such as transparent embryos (allowing time-lapse noninvasive imaging using labeled cell tracking), high fecundity, external fertilization, and rapid development. Moreover, significant genomic similarity with humans especially in the disease-associated genes and their ease of maintenance and cost-effectiveness have made them a cancer model of choice today. Zebrafish has been used in several areas of cancer research including establishing cancer models by chemical and genetic manipulation or manipulation by xenotransplantation, investigating angiogenesis and metastasis, identifying new targets for therapeutics, anticancer drug screening, etc. This chapter is focused on the use of zebrafish as a xenotransplantation model to study cancer biology such as proliferation, metastasis, and angiogenesis. The xenotransplantation of human cancer cells into zebrafish also has a huge application in drug discovery and in identification of drug targets. In this chapter, we describe various zebrafish xenotransplantation cancer models that have been established in adult zebrafish, juveniles, and embryos of the zebrafish. Lastly, we discuss the use of zebrafish xenotransplantation models for precision oncotherapy.KeywordsZebrafish xenotransplantationCancer biologyDrug screeningHuman xenograftsPrecision oncotherapy