Davide Pradella

The development of models to faithfully recapitulate human diseases, particularly cancer, has provided the groundwork for a better understanding of the mechanisms regulating tumor initiation and progression. Here, I describe an innovative strategy that combines the advantages of CRISPR/Cas9 technology and Cre-mediated recombination to engineer and track large focal amplifications mediated by ecDNAs observed in cancer patients (Pradella et al., Nature, 2025). Engineered oncogene-containing ecDNAs rapidly accumulate in primary cells, where they drive their immortalization and transformation. Even more relevant, this strategy has led to the generation of the first autochthonous preclinical mouse model of human cancer driven by a focal oncogene amplification. This novel approach will be valuable in investigating unresolved aspects of ecDNA biology and in developing new preclinical immunocompetent mouse models of human cancers harboring specific focal gene amplifications.

Davide Pradella is a Research Associate in Andrea Ventura`s lab at Memorial Sloan Kettering Cancer Center. His research interests are focused on a better understanding of extrachromosomal DNA (ecDNA) biology in cancer and its role in shaping tumor heterogeneity and evolution.