When Research on Canine Cancers Benefits Human Medicine

Given the difficulty of studying the development of certain human diseases, research sometimes turns to so-called animal models—ranging from zebrafish to chimpanzees. This raises a number of questions, both ethical and medical: Are laboratory rats or mice good models? A new drug that is effective in rodents will not necessarily be effective in humans… at least not at the same doses or in the same form. Hence the value of turning to larger models—literally—such as dogs. Dogs share not only their environment with humans but also genetic characteristics. The canine genome—that is, the complete set of its genes—has been fully sequenced since 2005. The analysis, conducted on a pedigree dog of the Boxer breed, identified just under 20,000 genes spread across 78 chromosomes, divided into 38 pairs of autosomal (non-sex) chromosomes and one pair of sex chromosomes (X and Y). Humans, by comparison, are said to have 23,000 genes spread across 23 pairs of chromosomes. Why study the canine genome? It’s all humanity’s fault… In fact, by selectively breeding more than 350 dog breeds for hunting, herding, protection, search and rescue, assistance to people, or simply as pets, we have also selected genes responsible for diseases. As a result, a large number of pedigree dogs have an increased susceptibility to complex genetic diseases such as cancers. And just as with us, alterations in a dog’s genome can have consequences for its health. Of the 500 genetic diseases that can affect dogs, half are analogous to those that affect us. Dogs could therefore, in theory, serve as good models… To the point of playing a major role in identifying new genes or developing innovative treatments? That’s what we’ll explore here.  

What Types of Cancers Affect Dogs?

As a beloved pet (even if cats have recently overtaken them in popularity), dogs are the subject of advanced medical monitoring. The data collected show that dogs spontaneously develop diseases similar to those that affect us: cardiovascular, autoimmune, and neurological diseases, among others. This is an advantage compared to mice, for example, where diseases are often artificially induced and only partially reflect human diseases. Cancer is one of the diseases that affect our pets. In fact, 25% to 30% of domestic dogs develop a malignant tumor. The most common are skin cancers such as mastocytoma or melanoma, mammary gland cancers in females, and lymphomas—cancers of the lymph nodes—which are also found in humans. Certain cancers are more common in specific breeds: mammary gland cancer in Dobermans or brain tumors in brachycephalic breeds (short-nosed dogs: Boxers, Bulldogs, Pugs, etc.). Under a microscope, the malignant cells in canine and human tumors look very similar. Similarities also exist at the genetic level: the same chromosomes or genes may be damaged. Recently, a comparative genomics analysis of the genome of a rare and poorly characterized human melanoma (mucosal melanoma) and oral melanoma in dogs—which is much more common—led to the discovery of similar genetic abnormalities between the two species. This discovery could lead to the identification of new treatments for both conditions.  

What is carcinogenic to us is also carcinogenic to our canine companions

Another health-related advantage of dogs is that they share our environment: the same living spaces, exposure to the same chemicals, the same stressors, and, until recently, the same diet. Smokers’ dogs are, unfortunately, a prime example of this. Smoking a cigarette exposes a dog to 4,000 chemicals, about 50 of which are carcinogenic. Dogs can be poisoned directly by inhaling cigarette smoke or indirectly through harmful tobacco-derived substances deposited on their fur and subsequently ingested. What happens next depends on the dog’s snout. Long-nosed breeds (Collies, Shetland Sheepdogs, etc.) will develop cancer of the nose or sinuses because the carcinogenic particles become trapped in their noses. Breeds with short or flat snouts (Bulldogs, Pekingese, Pugs, etc.), which lack a nasal filter, will see carcinogenic particles accumulate in their lungs, potentially causing lung cancer. Exposure to environmental toxins in dogs can be assessed using special collars that capture harmful particles, which can then be analyzed. Here again, research on dogs can contribute to a better understanding of human cancers.  

The Unique Features of the Canine Genomics

Interest in canine cancers surged following the canine genomics sequencing about fifteen years ago. A complete “reading” of the genome revealed surprising homogeneity, resulting from high levels of inbreeding within breeds. From one generation to the next, there is therefore very little genetic mixing, due to breeding practices designed to meet the criteria of each breed. In contrast, waves of migration and various human population flows have facilitated significant genetic mixing and resulted in a globally heterogeneous population composed of very different individuals. By breeding animals of the same breed together to fix physical characteristics, breeders have effectively eliminated many genes. But coat color and size were not the only traits selected; a predisposition to certain genetic diseases, including cancers, was also selected for. Virtually all dog breeds are affected by genetic diseases. These diseases often occur at a higher rate than in humans and can affect up to 10% of animals within certain breeds. Dogs thus represent a unique model for studying spontaneously occurring genetic diseases. But that’s not all. The homogeneity of the dog’s genome also makes it easier to identify the genes involved. Studying a monogenic disease (caused by a single abnormal gene) requires 20 affected dogs and 20 control (healthy) dogs. For a complex, multifactorial disease such as cancer, a few hundred animals are needed—in humans, several thousand patients and control subjects are required.  

A Benefit for Everyone

These figures underscore the value of dogs in deciphering the genetic basis of rare and/or complex diseases in humans. This concept of the “dog patient” benefits dogs first and foremost through the development of genetic tests and even effective therapies, and it benefits humans through the conduct of preclinical trials that assess the efficacy of proposed treatments… in dogs. Furthermore, since our canine companions have a shorter life expectancy, cancers develop and metastasize earlier in them—which allows for a rapid assessment of a new drug’s efficacy. Furthermore, adapting doses for humans is made easier by the fact that dogs are larger than rodents. This approach relies on close collaboration between researchers, veterinarians, physicians, and geneticists. The data obtained from these various cross-species studies can then be applied to homologous human diseases, with direct benefits for both species. According to the “One Health” concept, ensuring human health involves protecting the health of animals and ecosystems. In this context of interdependence, our pets serve as a mirror of our global health. Dogs are man’s best friend in more ways than one. Audrey Rousseau, Professor of Pathological Anatomy—Physician, Lecturer, and Researcher at Angers University Hospital, University of Angers, and Marie-Anne Colle, Professor of Veterinary Pathological Anatomy, Director of UMR PAnTher (UMR 703 INRAE/Oniris), INRAE     This article is republished from The Conversation under a Creative Commons license. Read the original article.