Pediatric cancer is a leading cause of death idraw n children and adolescents. Improvements in pediatric cancer treatment that include the alleviation of longterm adverse effects require a deeper understanding of the genetic, epigenetic, and developmental factors driving these cancers. Here, we review how the unique attributes of the zebrafish model system in embryology, imaging, and scalability have been used to identify new mechanisms of tumor initiation, progression, and relapse and for drug discovery. We focus on zebrafish models of leukemias, neural tumors and sarcomasthe most common and difficult childhood cancers to treat.
Childhood and Adolescent CancerPediatric cancer is one of the leading causes of death in children and adolescents (age 0-19 years) and is mainly comprised of leukemias, cancers of the nervous system, and sarcomas [1]. Recent genomic profiling efforts to better understand the etiology of this group of diseases have enabled the stratification of tumor types based on molecular signatures and have led to the identification of potential genetic drivers and cooperating molecular events that underlie the development of different pediatric cancers. Most pediatric malignancies are mutationally quiet and are thought to be driven by a single driver gene, a fusion oncoprotein, or structural/copy number alterations [2,3]. In contrast, adult tumors frequently exhibit high mutational burdens, likely due to a longer period of mutational acquisition under selective pressure [2,3]. Despite these differences, however, pediatric cancer treatments are still largely modeled after treatments designed for the adult version of the disease and can cause debilitating, long-term side effects when administered to children. The development of robust preclinical pediatric cancer models that accurately recapitulate these diseases will ultimately be necessary for the design of more precise, targeted therapies to improve outcomes for pediatric cancer patients. Here, we discuss how the use of zebrafish has advanced the pediatric cancer field as a preclinical model for gene and drug discovery.
HighlightsZebrafish develop tumors that are histologically and genetically similar to human tumors. Zebrafish enable the rapid identification of molecular drivers of tumor development and can be used to model cancers with unknown cells of origin using heatshock and β-actin promoters.Zebrafish models are amenable to highthroughput drug screening through larval drug submersion approaches, as well as transplantation of primary patient tumors into immunocompromised lines.Tumor-cell dynamics can be visualized in vivo throughout the lifetime of the animal by coupling oncogenes to fluorescent markers.