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

Deepika Dhawan,Christopher M Fulkerson,Noah M Hahn,Deborah W Knapp,Timothy L Ratliff

doi:10.1155/2017/6589529

Abstract

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune 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 traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

Highlights

With more than 7.5 million deaths from cancer worldwide each year, there is an ever increasing need to develop better cancer therapies, along with strategies to make cancer care more accessible
With the resurgence of immunotherapies and the understanding of the immune system’s role in many types of therapies [16,17,18], it is critical that animal models possess a level of immunocompetence similar to that in human cancer patients
There is a dire need for relevant animal models for research to improve the treatment and management of humans with invasive urinary bladder cancer (InvUC)

Summary

Introduction

With more than 7.5 million deaths from cancer worldwide each year, there is an ever increasing need to develop better cancer therapies, along with strategies to make cancer care more accessible. As summarized in this review, and using invasive urinary bladder cancer as an example, there is compelling evidence that pet dogs with specific forms of naturally occurring cancer can provide crucially needed relevant animal models to complement other models in preclinical research to help improve the success rate in human clinical trials [19, 20].

Results

Conclusion