The role of naturally-occurring canine tumors in translating conserved consequences of epithelial-mesenchymal plasticity to human cancers

Epithelial-mesenchymal plasticity (EMP) is a dynamic cellular process that confers motility to epithelial cells. In carcinomas, this program advances disease progression by promoting therapy resistance, recurrent disease, and spread to distant organ sites. The mechanisms of these clinical consequences are well studied in mouse models. However, mouse models lack physiologically relevant features of human cancers, including tumor heterogeneity, immune experience, and common environmental exposures. To address this, many groups have turned to naturally-occurring cancers in companion animals. This approach, known as comparative oncology, provides a model with conserved molecular mechanisms, similar environmental and immunological exposures, and realistic tumor heterogeneity. Moreover, companion animals receive the same treatment modalities as human patients and clinical trials can be executed with reduced cost and often in a shorter time frame. Therefore, studying EMP in companion animals, such as dogs, can help identify conserved features and therapeutic vulnerabilities. Here, we review consequences of EMP in four canine cancers: mammary, prostate, squamous cell, and urothelial carcinoma, with a focus on conserved features between murine models and disease in canine and human patients.