Spotlight on DOGBONe: Canadian Researchers Team Up to Fight Canine Osteosarcoma

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Spotlight on DOGBONe: Canadian Researchers Team Up to Fight Canine Osteosarcoma

Spotlight on DOGBONe: Canadian Researchers Team Up to Fight Canine Osteosarcoma

Meet the DOGBONe group at the University of Guelph Ontario Veterinary College.  Anthony J. Mutsaers DVM, PhD, DACVIM Oncology, Associate Professor at OVC shares with us the focus of the DOGBONe group, how the group came together, and how the group has evolved into an osteosarcoma multidisciplinary research team that shares samples, and is studying novel therapeutics for osteosarcoma.
Anthony J. Mutsaers DVM, PhD, DACVIM Oncology, Associate Professor at OVC
Can you tell us about the goals of the DOGBONe group and what was the impetus for starting it?

DOGBONe is an acronym for “Dog Osteosarcoma Group: Biomarkers Of Neoplasia”. It originally started out of the recognition that multiple investigators at the Ontario Veterinary College (OVC) from multiple departments, such as clinical studies, pathobiology, and biomedical sciences, were interested in obtaining samples from the canine osteosarcoma cases that were being treated at the OVC Mona Campbell Centre for Animal Cancer. The motivation to share samples has led to looking at data from the same cases through multiple platforms, depending on the interest and expertise of the investigators. Originally, the focus of the team was in areas such as circulating cytokines, genomics, microRNA, metabolism, extracellular vesicles, circulating tumour cells, and oncolytic virotherapy. It has been a great way to include investigators with multiple areas of expertise, and the group also includes faculty from the department of population medicine with expertise in statistical modeling. In addition, monthly group meetings facilitate sharing of research ideas, grant proposals, etc. The group has really evolved into an osteosarcoma multidisciplinary research team that exists independent of whether investigators require case samples to facilitate their work.

We have thought about expanding the name to also emphasize our efforts in studying novel therapeutics, but DOGBONe has really stuck, and we like it, so even though the group continues to expand with new investigators at OVC that study osteosarcoma (currently 4 more than the ones pictured on the stairs), including new members that focus on areas such as immunotherapy, immunogenic and autophagic cell death, the group name stays the same.

While osteosarcoma occurs at a much higher incidence rate in dogs than in humans, there are other cancers that are more common in dogs. Why did the group decide to focus on osteosarcoma?

There’s no question that the potential to make discoveries that could benefit both dogs and humans is a major motivating force to study canine osteosarcoma. Another aspect of this condition in dogs, besides how common it is, which facilitates ease of study, is the rather uniform presentation and outcome that exists. Most dogs have no detectable metastatic disease at the time they are diagnosed, and the primary tumour is removed, yet the vast majority develop metastasis at a predictable time following adjuvant chemotherapy treatment. I think this uniformity helps us understand when true clinical differences are made, as the extension of survival should be quite easy to appreciate.

How is working with canine samples similar or different to working with patient samples? Do you work with FFPE, frozen tissue and/or create cell lines and 3D models?

Working with canine samples is very similar to working with patient samples, right down to the process of informed consent that is required of the clients that bring their pet dogs to the hospital. We have a process of banking samples, run by the University of Guelph Institute for Comparative Cancer Investigation (ICCI), which collects FFPE, frozen samples, serum and urine, and keeps very good follow up on the outcome of cancer cases presenting to the clinic. Over 1000 samples have been collected and research partners have included academic and industry investigators across Canada and Internationally. We have also isolated multiple cell lines, including many from cases of canine osteosarcoma, from both primary tumour and metastatic sites.

One challenge in working with mouse models is the lack of an immune system to be able to study human immunotherapies and immune response.  Do dogs have a similar immune system to humans?

The immune system in the dog is very similar to humans. This has been beneficial from the standpoint of being able to include the possible contributions of the immune system to tumour responses to a variety of therapies. In addition, it also means that breakthroughs in immunotherapy for humans, such as immune checkpoint inhibitor therapy, may be designed to be applied in dogs with the naturally-occurring disease. Biotechnology is at a place where applying these advances across species is increasingly possible.

Can you tell us about any biomarkers that have been identified to date?

While there are many areas being pursued, particularly in the areas of microRNA and extracellular vesicle profiling, I have been directly involved in the cytokine analysis area, which has recently revealed a prominent association between the levels of circulating CXCL10 (as well as IL-8) and disease outcome. Given the access to samples and great follow up data, we were able to examine blood samples before and after primary tumour treatment, as well as during chemotherapy and progression. Now, we will be able to dig deeper into what these associations may mean for the underlying biology, case stratification, and/or therapies (immunotherapy or otherwise).

Some common gene mutations in human osteosarcoma are p53, MYC, RB1, ATRX, CDKN2A, CDKN2B - do any of these overlap with common canine osteosarcoma mutations?

Yes, many of the genomic changes in osteosarcoma translate well across humans and dogs. Even if the specific mutations are not the same, the affected pathways appear to be identical in many cases.

There seem to be so many advantages to using dogs as a "model" for studying human osteosarcoma.  Are there some things that don’t translate well between dogs and humans?

One thing that always sticks in my mind about studying dogs as a model for human osteosarcoma is the age discrepancy. Despite a smaller, younger cohort of cases, most dogs that get this diagnosis are middle-aged and older, which is a stark contrast to human osteosarcoma. The condensed lifespan of the dog means we get results of our studies quickly, and despite the similarities we currently know regarding the genomics of osteosarcoma in both species, these changes take longer to occur in the dog, relatively speaking. 

We saved the most important question for last! Do you have a dog and please share details and a pic!

I’m actually between dogs at the moment. Our household currently includes 2 cats, and we have a hobby farm with 4 horses. Our cat Milly appears more than happy to assume the role of ‘family dog’, as she plays fetch relentlessly. Despite her likely preference to maintain the house the way it is currently, I expect we’ll come across our next dog soon. In the meantime, when I am on clinic duty I work with over a dozen great pets (and clients) daily, most of which are dogs, which is a very nice way to spend a work day.

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