Learning cancer genetics from domestic cats.

The domestic cat (Felis catus) shares key biological features with humans, including susceptibility to tumor development. Genomic analysis of 493 feline tumors across 13 histologically defined types revealed striking similarities but also differences to human cancers. These feline tumors arose spontaneously in immunocompetent hosts and environmentally relevant settings, which is reminiscent of the human disease. Like in human cancers, mutations in the tumor suppressor TP53 were frequently detected. In contrast, tumor-promoting gain-of-function point mutations in the RAS gene were not found in feline tumors. Functional studies demonstrate translational potential, such as high sensitivity of FBXW7-mutated feline tumoroids to vinca alkaloids. Despite challenges, including variable life histories of affected cats and significant differences in the metabolism of cats and humans, feline oncology could provide important comparative insights into cancer biology and therapeutic vulnerabilities.