Fusion oncogenes in cancer: organoid models and novel therapeutic approaches

Oncogenic fusions, arising from chromosomal rearrangements, occur in several cancers, particularly in those of pediatric origin. Advances in sequencing technologies have improved fusion detection; yet, understanding their mechanisms and tumorigenic potential remains challenging. This is partly due to the limited availability of faithful human-based model systems. Organoids have emerged as a physiologically relevant model system with in vivo-like traits and have recently allowed to obtain novel mechanistic and therapeutic insights for oncogenic fusion-bearing cancers. This review discusses how, through bottom-up tumor modeling as well as tumoroid derivation, these models are being employed to increase our understanding of fusion-bearing cancers, and how they can help future therapeutic discovery for these tumors.