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Would your dogs benefit from targeted health treatment and prevention plans tailored to their unique physiology? Would you like to work with your dog’s veterinary team to determine the most effective medical treatments with the highest safety margins?
Personalized medicine, also known as precision medicine, is poised to do just that. The field of personalized medicine is flourishing in human and veterinary healthcare, and the AKC Canine Health Foundation (CHF) and its donors are funding research to advance the health of all dogs on a personal level.
CHF-funded researchers recently published a review article in Human Genetics [1], summarizing the presence and impact of known genetic variations affecting drug metabolism in dogs. They also discussed precision medicine in canine cancer treatment and offered considerations for canine pharmacogenetics testing.
While veterinarians have long known about breed sensitivities to various drugs, improvements in genetic technologies mean that we can now more fully study the spectrum of genes that may be involved in an individual dog’s response to drugs.
These pharmacogenomic studies can improve our understanding of why and how individuals respond to drugs differently – either with toxicity or a failure to respond – in dogs and humans. There are multiples examples within this review of pharmacogenomic research benefitting dogs.
Multiple Drug Resistance
The multiple drug resistance, or MDR1, gene mutation has been called the single most ‘very important pharmacogene’ (VIP) in dogs. A specific mutation results in a non-functional P-glycoprotein transporter protein. Since transporter proteins function to move substances out of the body or away from sensitive tissues, a decrease in their function alters the safety and efficacy of drugs in affected patients.
The MDR1 mutation is relatively common and has been described in herding breeds, sighthounds, numerous mixed–breed dogs, and other breeds. Affected dogs show extreme sensitivity to drugs such as the commonly-used parasiticide ivermectin, chemotherapy drugs such as vincristine and doxorubicin, and others. Thanks to important research on this mutation, it is now standard practice in veterinary medicine to test for the MDR1 mutation before using P-glycoprotein transported drugs in dogs of potentially affected breed origin.
Sighthounds and Anesthesia
Genetic mutations that alter the function of Cytochrome P450 enzymes are suspected to contribute to the prolonged recovery seen in sighthounds (particularly Greyhounds) after administration of injectable anesthetics such as thiopental and propofol. Cytochrome P450 enzymes are located primarily in the liver and intestinal mucosa and are critical for drug metabolism and elimination in dogs and people. Genetic mutations that affect these enzymes result in great variation in an individual’s ability to metabolize certain drugs.
With grants awarded by CHF, studies on this topic are underway. Grant 02242: Understanding the Genetics of Adverse Drug Reactions in Sighthounds allowed Washington State University researchers to identify two mutations in sighthounds and Border Collies that decrease drug metabolism in vitro (such as in a test tube or culture dish). Their research continues, with CHF Grant 02529, as the investigators work to prove that these mutations affect drug metabolism in dogs. Results will hopefully lead to a drug sensitivity test to identify affected dogs and guide the safe use of drugs in these veterinary patients.
Personalized Medicine For Canine Cancer
Precision medicine research for canine cancer takes a different approach. Instead of looking for genetic mutations that predict adverse drug reactions, these studies identify mutations in tumor DNA that are not present in the host DNA and can, therefore, be used as treatment targets.
An example of personalized cancer medicine in dogs is the treatment of mast cell tumors with the drug toceranib (Palladia®). Toceranib is a receptor tyrosine kinase inhibitor, and dogs with mast cell tumors containing a specific c-kit gene mutation are more likely to respond to this drug compared to those without the mutation.
Mast cell tumor prognostic panels which test for this c-kit mutation and others are now available. Additional research, such as the study funded by CHF Grant 01426: Personalized Medicine for the Treatment of Canine Mast Cell Tumors, may also help determine the best treatment options for dogs affected by mast cell tumors.
Researchers are also developing a diagnostic tool that may rapidly describe the mutational profile of canine lymphoma with funding from CHF Grant 02502: Precision Medicine for Canine Lymphoma. They are exploring mutations in canine lymphoma biopsy samples to guide the selection of the most effective treatments and determine if such mutational profiles predict clinical outcome.
Improving Treatment Options For Your Dog
As genetic studies continue to improve our understanding of individual variations in drug response in dogs, scientists continue to urge caution. Pharmacogenetics is a relatively new field in veterinary medicine, and results must be interpreted by a veterinarian with adequate training in clinical pharmacology and genomics.
CHF remains committed to funding studies with the highest scientific standards that have the greatest potential to advance the health of dogs. Research that improves our understanding of how an individual dog will respond to a particular drug or that identifies the best treatment for a dog with a specific illness means a continued shift toward personalized veterinary medicine. CHF and its donors are working together to ensure that all dogs live longer, healthier lives.
Important Updates on AKC Canine Health Foundation (CHF) Funded Research:
Clinical Trial for Hemangiosarcoma in Dogs
CHF Grant 02534: Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma provides funding for a multi-institutional clinical trial to establish whether propranolol in combination with standard care will improve outcomes for dogs with hemangiosarcoma. Recent studies in people with a similar tumor, angiosarcoma, showed that propranolol, a common drug used to treat heart disease in humans and dogs, increased the survival time for human angiosarcoma patients. Propranolol was also shown to sensitize hemangiosarcoma cells to chemotherapy, providing a more effective way to kill tumor cells.
Participation requirements for this clinical trial at the University of Minnesota are available here.
Resources
- Mealey, K.L., Martinez, S.E., Villarino, N.F. et al. (2019) Personalized Medicine: Going to the Dogs? Hum Genet, 138: 467. https://doi.org/10.1007/s00439-019-02020-w
For more current medical news, view the latest CHF fact sheets at akcchf.org/tophealthconcerns.