Urinary Bladder Cancer in Dogs: A Promising Model for Advancing Human Urothelial Carcinoma Research?

Abstract

Dogs are widely recognised as valuable models in comparative oncology because they develop cancer spontaneously, have shorter lifespans, and share significant biological and clinical similarities with human tumours. The objective of this review was to assess the relevance of canine urothelial carcinoma (UC) as a translational model for human bladder cancer by comparing epidemiological patterns, molecular alterations, and immunological features across species. Urothelial carcinoma is of particular interest due to its aggressive nature and high mortality rates. In dogs, invasive forms of UC are more common, underscoring the relevance of this species for modelling human disease. While advanced age and exposure to environmental carcinogens are shared risk factors, notable epidemiological differences exist, including a higher prevalence in female dogs than in male humans. Molecularly, canine and human UCs share tumour subtypes and dysregulation of key oncogenic pathways, such as p53/p63, RTK/RAS/MAPK, PI3K/AKT/mTOR, and CDKN2A/CDK4, despite distinct initiating genetic events. These alterations converge on pathways controlling proliferation, survival, and immune evasion. Shared overexpression of therapeutic targets and similar immune checkpoint mechanisms further support the translational value of the canine model. Collectively, these features reinforce the utility of dogs in advancing biological understanding and therapeutic development for urothelial carcinoma in both veterinary and human medicine.