Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

摘要

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targetsin cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditionalexperimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, andimmune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however,that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditionalmodels. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancerin humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, andresponse to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that inhumans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating importantfindings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targetedtherapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.