Naturally occurring diseases in animals: contributions to translational medicine.

Abstract

T he natural world brings to us an array of opportunities to understand the processes of life and disease. Naturally occurring or spontaneous diseases of animals allow us to gain important and fundamental knowledge of human disease and translational medicine. This edition of the ILAR Journal brings together a number of reviews that enlighten us about naturally occurring diseases of animals. These reviews are written in context to lessons learned about disease processes and translating this knowledge to the treatment of human disease. Among these articles are well-documented examples of animal diseases with causes ranging from genetic to infectious. Importantly, these natural animal models provide insight into the pathogenesis of human maladies and offer unique perspectives of how this information can be applied to intervention strategies in people. Naturally occurring cancers in dogs provide interesting parallels in our understanding of human cancers. Dr. Alvarez’s article on naturally occurring canine cancers provides a current view of the advantage of studying canine cancer to understand the genetic basis of human cancers. Although mouse models are clearly a preferred model for genetic manipulation throughout biomedical science, the canine naturally selected model provides opportunities to study the causes of cancer in context of the same environment as their owners. Dogs provide a novel model in this setting, in part, because of purposeful genetic breeding that amplifies phenotypes pleasing to humans. The reduced generation time of dogs and recent knowledge of the canine genome have accelerated the usefulness of dogs as models of human cancer. The canine cancer model is further focused on in the review by Drs. Fenger, London, and Kisseberth, who document the parallels between canine osteosarcoma and sarcomas in children. Osteosarcoma is the most common malignant bone cancer in children and dogs. Although conventional treatments have greatly improved the survival of children and dogs suffering from osteosarcoma, new treatments are required to further extend the success of therapies against this aggressive cancer. The authors point out the important parallel clinical and biological features of human and canine osteosarcoma. At the molecular level, the canine cancer parallels what we know about pediatric osteosarcoma, making the dog model particularly relevant in the development of new targeted drugs against the cancer. This theme continues in the review by Dr. Knapp and colleagues of bladder cancer in dogs and humans. Urinary bladder cancer affects thousands of human and canine patients each year. Naturally occurring bladder cancer in dogs has many similarities to invasive bladder cancer in humans at the cellular, molecular, and biological levels, making this naturally occurring model attractive to study new forms of therapy against this deadly cancer. This review illustrates the value of combining knowledge about canine bladder cancer with that of induced rodent models to help guide translational approaches to understanding invasive urothelial carcinoma of humans. Bladder cancer studies in dogs have the potential to define heritable and environmental risks for the human disease. In addition, recent clinical trials in dogs suffering from transitional cell carcinoma serve the dual purpose to improve the lives of pet dogs and to inform human clinical trials. Drs. Davis and Ostrander provide an insightful overview of the value of understanding naturally occurring cancers in dogs from a genomics perspective. With more than 70 million pure and mixed breed dogs in the United States, combined with the fact that cancer is a leading cause of death in this species, the value of understanding the genetics of dog cancers is dramatic. As knowledge of the canine genome and of specific mutations in their cancers expands, so too have opportunities to clarify the underlying causes of cancer in people suffering similar cancer types. Improvements in the care of dogs have paralleled their owner’s willingness to seek out new treatments for dog cancers. Through the careful evaluation of breed tendencies, combined with surveys of specific genetic mutations, researchers have provided a new avenue to understand the causes of cancer in both humans and dogs. This review illustrates that genomic analysis in pet dogs may offer new insights Michael D. Lairmore, DVM, PhD, is Professor and Dean at the University of California-Davis, School of VeterinaryMedicine in Davis, California. Chand Khanna, DVM, PhD, is Head of the Tumor and Metastasis Biology Section and Senior Investigator at the Center for Cancer Research in Bethesda, Maryland. Address correspondence and reprint requests to Michael D. Lairmore University of California-Davis, School of Veterinary Medicine, One Shields Avenue, Davis, California 95616 or mdlairmore@ucdavis.edu