Invasive urothelial carcinoma (InvUC) of the urinary bladder is an aggressive malignancy affecting both dogs and humans. In this review, the authors argue that dogs with naturally occurring InvUC offer a uniquely powerful comparative oncology model capable of bridging critical gaps between traditional preclinical studies and human clinical trials.
Modern cancer drug development increasingly relies on genomic targeting, epigenetic modulation, and immunotherapy. However, widely used experimental models—such as rodent xenografts—often fail to replicate the tumor heterogeneity, molecular complexity, immune interactions, and metastatic behavior observed in human cancers. These limitations contribute to high failure rates in late-stage human trials.
The authors highlight that naturally occurring canine InvUC closely mirrors the human disease in multiple dimensions, including histopathology, molecular alterations, patterns of invasion and metastasis, and response to chemotherapy. Importantly, canine tumors develop spontaneously in immunocompetent hosts, allowing realistic evaluation of tumor–immune system interactions.
Genomic analyses reveal striking similarities between canine and human InvUC, including shared oncogenic pathways and actionable molecular targets. These parallels have enabled canine clinical trials to test targeted therapies and novel agents under conditions that closely approximate human clinical reality.
The review summarizes several successful canine trials that have directly informed human oncology research, demonstrating how therapeutic signals observed in dogs can predict efficacy or toxicity in people. At the same time, the authors discuss challenges that must be addressed, including trial harmonization, regulatory alignment, funding structures, and integration of veterinary and human oncology efforts.
Overall, the authors conclude that incorporating dogs with naturally occurring InvUC into the drug development pipeline can increase the predictive value of preclinical testing, reduce costly human trial failures, and simultaneously advance veterinary cancer care. This dual-benefit framework exemplifies the promise of One Health and comparative oncology approaches.
Source: Fulkerson, C. M., Dhawan, D., Ratliff, T., Hahn, N., & Knapp, D. (2017). Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs. :contentReference[oaicite:1]{index=1}.
