Pediatric Cancer Models in Zebrafish

Abstract

Pediatric cancer is a leading cause of death in children and adolescents. Improvements in pediatric cancer treatment that include the alleviation of long-term 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 sarcomas - the most common and difficult childhood cancers to treat.

Keywords: brain tumors; cancer; leukemia; pediatric; sarcoma; zebrafish.

Figure 1. Key Figure.. Frequency of Pediatric Cancers and Corresponding Anatomical Location in Zebrafish.

The frequency of childhood (inner circle) and adolescent (outer circle) cancers (as reported in [11,36]) with corresponding anatomical tumor location in zebrafish is illustrated. Zebrafish models have been developed for pediatric leukemia, brain tumors, sarcomas, germ-cell tumors and neuroblastoma (bolded). Representative histology of these zebrafish models is shown on the right. Histology images from: [26] (T-ALL), [39] (CNS-PNET), [62] (ERMS), [71] (Germ-Cell Tumor), and [50] (NB).

Figure 2:. Comparison of Zebrafish and Mouse Models of Pediatric Cancer.

Zebrafish and mouse models of pediatric cancer have complementary attributes for identifying new mechanisms driving childhood tumors. Both model systems have conserved developmental and oncogenic pathways, can be utilized for PDXs, and have genome-editing technologies available. Zebrafish have unique advantages in scalability, cost and imaging. In contrast, mice have conserved physiological features (body temperature and organ systems) and more accurate drug delivery, dosing and metabolism.