Fish Metastasis Atlas for the Systematic Analysis of Organ-Specific Dissemination of Cancer

Metastasis is a multifaceted process in which cancer cells must overcome diverse biological barriers to establish secondary tumors and drive disease progression. Different cancers exhibit highly non random, organ specific patterns of dissemination, known as organotropism, which arise from cancer cell plasticity and interactions with the host microenvironment. A major challenge in the field is the lack of approaches that capture cancer cell dissemination at the whole organism scale while maintaining physiological relevance. Here, we introduce an in vivo zebrafish model coupled with a data driven computational framework to systematically map and compare patterns of cancer dissemination. Using patient derived Ewing sarcoma cell lines, global analyses reveal pronounced heterogeneity across individual cell lines, which are further resolved by local metrics that capture region specific colonization frequency and cancer cell visit density. This combined global-local approach identifies recurrent spatial preferences across the fish body and uncovers correlated organ targeting, indicating coordinated and structured dissemination dependent on cancer cell line and disease stage. The framework is robust and adaptable to diverse imaging datasets, providing a scalable platform for studying cancer-microenvironment interactions and spatially organized metastatic behavior for various cancer types as well as genetic and drug perturbations, with potential relevance for personalized treatment strategies.