Personalized Zebrafish Models for Fusion-Positive Pediatric Sarcomas

Clinical sequencing efforts have revolutionized our approaches to categorizing pediatric cancers in real time. This has dramatically improved our ability to profile pediatric tumors, identify actionable vulnerabilities, and influence clinical care. However, often many of these genetic drivers are indicators of poor prognosis with no available targeted therapies. This is especially true for fusion-positive pediatric sarcomas, which are driven by defining oncogenic fusions that are often intractable therapeutically. Additionally, many of these fusions have no cell, animal, or patient-derived xenograft models to understand the biology of the human disease, hindering our ability to find new therapeutic opportunities. Here, we present strategies for linking personalized genomics to precision medicine approaches using zebrafish models as a proxy to understand human disease on a high-throughput scale. Our vision for the future involves integrating this vertebrate model system to directly influence clinical care.