November is Pet Cancer Awareness Month, a time to reflect on the challenges faced by our furry companions battling this disease and how they help make it better for human osteosarcoma patients. The incidence of osteosarcoma in dogs is estimated to be ten times higher than in humans, underscoring the importance of comparative oncology, where insights gained from veterinary cases can significantly advance our understanding and treatment of cancer in human patients.
This month we spotlight the Flint Animal Cancer Center at Colorado State University, a leading institution dedicated to the study and treatment of cancer in animals. Their innovative research and clinical practices not only aim to improve outcomes for pets but also hold potential to unlock breakthroughs that can benefit human patients. Doug Thamm, VMD and Dan Regan, DVM, PhD lead the clinical and research programs respectively and they share with us the philosophy behind the One Cure goal to improve the prevention, diagnosis, and treatment of cancer in pets and then use that research and knowledge to also benefit people with cancer.
The Flint Animal Cancer Center offers clinical care, conducts research, and is a teaching facility. How do these different functions interact with each other?
Teaching is one of our core values and we aim to empower the next generation of researchers and clinicians. We are a bit unique in that we strive for integration of clinical and bench research into our veterinary training programs. Our 4th year veterinary students participate in twice-daily rounds where all aspects of clinical care, including clinical trials, are routinely discussed. Our oncology house officers (interns and residents) spend approximately 15% of their clinic time rotating through our oncology clinical trials service, and the house officers are strongly encouraged to pursue both bench and clinical research experiences during their training. We also are fortunate that our clinical space and our research labs are adjacent to each other in an NIH-style arrangement, which facilitates clinical to laboratory translation and interactions. On the flip side, it is common for some of our graduate students and postdocs to work closely with the clinical team on translational questions, which adds another layer of integration.
Can you describe the field of comparative oncology, the founding principle of the One Cure initiative, and its significance for pediatric cancer research?
Comparative oncology is an approach to studying cancer based on the principle that pet dogs with cancer provide an unparalleled opportunity to improve the efficiency of cancer drug discovery and clinical therapeutic development. This field is built upon foundational work demonstrating that canine tumors share many biological, genetic, and histologic features with their human tumor counterparts, and most importantly, retain the complexities of naturally occurring drug resistance, metastasis, and tumor-host immune interactions, all of which are difficult to recapitulate in induced or genetically engineered mouse models. The utility of naturally occurring cancers in companion animals has been particularly apparent in sarcoma research, where the increased incidence of sarcomas in dogs as compared to people has facilitated comparative research that accelerated treatment advances benefitting both species. One Cure is really founded upon this latter point and the belief that cancer is cancer - if veterinarians, physicians and Ph.D. scientists work together, learn from each other, and leverage this comparative oncology approach as another tool in cancer research, that we can improve our odds/reduce the time to finding cancer treatment breakthroughs.
How prevalent is osteosarcoma in dogs?
High quality statistics about the prevalence of different canine cancers are hard to come by and hampered by the fact that many canine osteosarcoma cases may never have a firm diagnosis. Some estimates put the incidence at around 14 per 100,000 dogs, which is more than 10 times higher than the human incidence. And this is probably an underestimation. To put this in perspective another way, the national incidence of osteosarcoma in humans is around 800 cases per year. Just here at the Flint Animal Cancer Center, we see around 100 cases per year in dogs.
What do canine and human osteosarcoma patients have in common?
A lot! Both species develop tumors at similar timepoints in their lifespans – early in age and again later in life. These tumors typically occur in the long bones/limbs of both species, and while there are some key differences in treatment (neoadjuvant chemo in people, MAP three drug protocol vs. single agent chemo in dogs), for the most part both dogs and people with osteosarcoma are treated similarly– surgery to remove the primary tumor and then adjuvant cytotoxic chemotherapy, with the two most commonly used drugs being the same in pets and people. Both canine (and their owners!) and human patients have to endure this long and difficult treatment regime of surgery, multiple infusions, many recheck exams, and the constant anxiety of monitoring for most patients, tumor recurrence. And ultimately, our ability to delay this recurrence or treat this recurrent disease has led to a decade’s long stagnation in outcomes for both species.
Aside from some of the similarities between canine and human osteosarcoma patients that you already mentioned, what are some aspects unique to canine osteosarcoma patients that make them a great patient population to study this rare disease?
Dogs can be excellent models for other aspects of osteosarcoma care like surgical and radiation therapy interventions, as well as imaging techniques, thanks to their large body size. We use human clinical equipment in our hospital for surgery, radiation therapy and imaging – no need to miniaturize or adapt these techniques like what might be required in rodents, so the translation can theoretically be a bit more seamless. Another important consideration is the clinical care that our patients receive. Unlike rodents or even laboratory dogs, our patients, whether receiving conventional clinical treatment or investigational therapy, receive intensive supportive care (anesthesia monitoring, pain control, nausea and appetite management, intensive care support when necessary), which also much more closely approaches the human standard of care. We have validated and nearly universally accepted grading criteria for things like adverse events and tumor responses, which also closely parallel the human systems.
What are some of the differences in canine and human patients that result in different treatment protocols for each patient population?
We commonly hear that cancer treatment in our patients must be a lot like treating very young pediatric patients, because neither group of patients can talk to us and communication and treatment decisions take place through the caregivers. While this is certainly true, there’s another way in which veterinary oncology might more closely resemble human geriatric oncology – we may use protocols that are less intensive in an attempt to preserve quality of life, ensure that our patients stay out of the hospital, address their comorbidities, etc. This translates into reduced dose intensity, which may be a major contributor to the less positive outcomes in most of our canine osteosarcoma patients.
How do comparative oncology researchers share learning and pass the translational baton to pediatric cancer researchers?
I think networking and community building, building awareness of the strengths (and limitations) of the comparative oncology approach is paramount. This needs to happen through grass roots efforts – reaching out to individual investigators, attending each other’s scientific meetings (DVMs at CTOS, FACTOR, MDs at VCS etc.), joining cross-disciplinary working groups, a fundamental openness to collaboration and innovative thought, centralized and open access data sharing. DVMs need to work with MDs to fully understand the gaps in knowledge for the human disease so that they know how best to leverage dogs and design comparative oncology trials to appropriately answer some of these key questions. Continued efforts in diversification of our cancer research workforce training and infrastructure – improved opportunities for cross-disciplinary training of veterinarians and physicians.
Technology is rapidly advancing research and treatment possibilities from single-cell RNA sequencing and liquid biopsies, to local control options. Where do you see the most potential for progress in the next five years?
In osteosarcoma, I think it is in identifying upfront biomarkers which predict chemotherapy response and/or disease recurrence. The field is in dire need of easily employed upfront biomarkers for patient risk stratification. I think these rapidly advancing/emerging technologies are finally positioning us to identify these in osteosarcoma, and I think their identification can be accelerated with a cross-species approach. Many other tumor types have such biomarkers, one is emerging in OS (MYC perhaps?) but I think we are primed to really dig in and start to better solve this puzzle.
