Developmental Modeling of Childhood Cancers.

Growing evidence indicates that childhood cancer is a developmental disease and the oncogenic impact of mutations depends on spatiotemporal developmental contexts. This dependency leads to distinct molecular, genetic, and clinical characteristics across various cancer (sub)types. However, the underlying molecular mechanisms of tumorigenesis are not fully understood, and the development of precision medicine for childhood cancers is still an ongoing effort, partially due to their relative rarity. Therefore, it is crucial to develop and use "developmental models" that replicate both mutations and specific developmental contexts that determine their impact. In this review, we summarize recent advances in the growing field of developmental modeling of childhood cancers, which enhance our understanding of the pathogenic mechanisms and pave the way for the development of new therapeutic approaches.