Simon R. Platt
BVM&S, MRCVS, DACVIM (Neurology), DECVN
University of Georgia
College of Veterinary Medicine
Simon R. Platt, BVM&S, MRCVS, DACVIM (Neurology), DECVN, is a professor of neurology and neurosurgery at University of Georgia College of Veterinary Medicine. His research interests include ischemic disease of the central nervous system, canine brain tumors, and epilepsy.
Dr. Platt is a member of the International Veterinary Epilepsy Task Force and a founding member of the Southeastern Veterinary Neurology Group. He has authored or coauthored more than 190 journal articles and 50 book chapters and is the co-editor of three textbooks: BSAVA Manual of Canine and Feline Neurology, Manual of Small Animal Neurological Emergencies, and Canine and Feline Epilepsy: Diagnosis and Management. Dr. Platt received his veterinary degree from University of Edinburgh (Scotland) and completed an internship in small animal medicine and surgery at Ontario Veterinary College (University of Guelph) and residency in neurology and neurosurgery at University of Florida.Read Articles Written by Simon R. Platt
Much has been made of the recognition that animal health and human health have a multitude of parallels. Throughout many species, diseases have been documented and researched, and they share a plethora of similarities with the same diseases in humans. These similarities may be pathologic, genetic, or pathophysiological, creating windows of opportunity to investigate new diagnostic and therapeutic strategies that may potentially benefit animals, as well as humans, with a given disease.
Across the world, unions have formed between veterinary and human medicine teams under One Health directives and they are exploring the “naturally occurring” models of human disease that dogs and cats, for instance, now represent.
Shortcomings of Rodent Research Models
Oncologic diseases are just one group of health issues being investigated in dogs on a cytogenetic, diagnostic, and therapeutic basis. Many cancers in humans have retained their poor prognoses over several decades despite billions of dollars of investment into the use of murine models of these diseases. While these artificially created models, or “living Petri dishes,” have helped advance the understanding of cancers on histologic, molecular, and cytogenetic levels, they have consistently failed to identify “game changing” therapies in many of the most devastating cancers.
The main reason for this failure is that artificial rodent tumor-bearing models do not adequately reflect human tumor biology or tumor heterogeneity, and they may demonstrate different drug metabolism characteristics than tumors in humans.1 Rodent models often lack a competent immune system and their tumors often respond differently to cancer treatments than human tumors.2 Additionally, such small animals are inappropriate models to accurately evaluate novel treatments in conjunction with standard surgical resection.
“ Our essential connection with animals is ancient, and it runs deep. It extends from body to behavior, from psychology to society—forming the basis of our daily journey of survival. This calls for physicians and patients to think beyond the human bedside to barnyards, jungles, oceans, and skies. Because the fate of our world’s health doesn’t depend solely on how we humans fare. Rather it will be determined by how all the patients on the planet live, grow, get sick, and heal.”
(Barbara Natterson-Horowitz & Kathryn Bowers, Zoobiquity: The Astonishing Connection Between Human and Animal Health)
Dogs Are More Than Man’s Best Friend
Spontaneous “naturally occurring” cancer models offer an opportunity to apply a “comparative” perspective with translational applications to new drug discovery and development.3 We are all aware that dogs have a long history in biomedical research, based on their strong anatomical and physiological similarities to humans; the relatively high number of pet dogs that are diagnosed and treated with cancer each year have focused attention on this species.
Investigations of cancer in dogs have been pursued for over 40 years,4 but to date they represent an under-utilized model, one with an intact immune system that is more genetically outbred. The recent deciphering of the canine genome provides evidence of strong similarities with humans, particularly with respect to the gene families associated with cancer, which are significantly closer than the relationship between mice and humans.4-6
Clinical Trials Provide Treatment Options
Of significant advantage to the pursuit of One Health goals is that many dog owners are highly motivated and will often seek out new options for the management of cancer in their pets; many will have interest in receiving care that is provided as part of clinical trials when conventionally available treatments do not meet their goals.
Recent centralization of clinical trial information has been made available through the efforts of the American Veterinary Medical Association and can be viewed at ebusiness.avma.org/aahsd/study_search.aspx. This website provides a place where veterinarians and owners alike may search for clinical trials that are studying any number of canine health issues, including cancer.
Most of the trials are funded, which implies that there is a considerable financial incentive for the owner to pursue a treatment that may previously have been too expensive to consider.
First, Do No Harm: Considerations for Clinical Trials
However, we must keep in mind several important issues that need to be front and center of any discussion surrounding use of a pet in a medical trial for the benefit of veterinary and human medicine.
First and foremost, we are dealing with a family member and, although it can be easily accepted that novel treatment strategies will be unproven in their success, it is difficult to justify use of an untested treatment if its safety cannot be guaranteed due to lack of sufficient preliminary data in this species.
Second, success in many clinical trials evaluating cancer therapies in humans is based upon survival. This is a flawed marker of outcome in veterinary medicine, as we all know that quality of life and owner input determine survival in pet dogs. Therefore, other, perhaps less well-defined, markers need to be used, potentially detracting from the pure translational information that the trial can provide.
Third, veterinary medicine can rarely offer a significant number of clinical cases for enrollment in these trials, which means that the resulting data documenting success is not very robust. Yet there is value in these clinical trials that must not be underestimated; it’s just that our expectations must be set appropriately.
If this approach is thoughtfully achieved, our pet dogs can represent a valuable stepping stone in the battle to find better therapeutics in humans. In the interim, such financially supported studies can help some dogs that would otherwise have had no feasible treatment options.
Success in clinical trials can help the species as a whole, which is the bystander effect that interests us veterinarians the most, as it directly benefits our own patients.
- Huszthy PC, Daphu I, Niclou SP, et al. In vivo models of primary brain tumors: Pitfalls and perspectives. Neuro Oncol 2012; 14:979-993.
- Candolfi M, Curtin JF, Nichols WS, et al. Intracranial glioblastoma models in preclinical neuro-oncology: Neuropathological characterization and tumor progression. J Neurooncol 2007; 85:133-148.
- Hansen K, Khanna C. Spontaneous and genetically engineered animal models; use in preclinical cancer drug development. Eur J Cancer 2004; 40:858-880.
- Paoloni M, Khanna C. Translation of new cancer treatments from pet dogs to humans. Nat Rev Cancer 2008; 8:147-156.
- Lindblad-Toh K, Wade CM, Mikkelsen TS, et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 2005; 438:803-819.
- O’Brien SJ, Murphy WJ. Genomics. A dog’s breakfast? Science 2003; 301:1854-1855.