When it comes to cancer, man and his best friend are not that different. With similar genomes and shared environmental triggers leading to spontaneous tumors, dogs can throw us a bone or two when it comes to unraveling the mysteries surrounding cancer. To promote the collaborative study of human and canine cancers, Duke Cancer Institute (DCI) and North Carolina State University’s (NCSU) College of Veterinary Medicine have teamed up to establish the Consortium for Canine Comparative Oncology, which hosted its first symposium on March 4.
Michael B. Kastan, MD, PhD, executive director of Duke Cancer Institute, said successes from partnerships in comparative oncology, like those at the symposium, will foster a collaborative culture between oncologists studying both patient populations. “We want to set a standard which everyone else wants to emulate, and we are hoping that this could be a national movement,” he said.
With that mission, DCI is extending membership for collaborating faculty from other institutions involved in cancer research with access to all shared resources. A Joint Institution Funding Opportunity up to $100K is also offered for pilot projects. “We need to keep the foot on the pedal in order to keep moving things forward. It’s not something that just happens organically because of people’s interests.”
In her keynote address, Amy LeBlanc, DVM, director, NCI Comparative Oncology Program, said that comparative oncology’s big challenges included acceptance by key stakeholders in drug development and development of platforms to support translation across species. “We are poised to make huge improvements in how comparative oncology can contribute to the field,” she stated.
Across the tree of life, cancer is a delicate balance between multicellular cooperation and cellular cheating to escape this organization, said William Eward, DVM, MD, comparative oncologist from DCI. Therefore, analyzing genomic clues across different species can reveal evolutionarily conserved genetic mechanisms that drive tumor formation. For instance, canine cancers show many molecular parallels with their human counterparts. Non-Hodgkin lymphomas in humans and dogs share gene expression subtypes, similar cell surface markers, and even common driver mutations such as Myc translocations. Canine and human melanomas share similar biological behavior and immunologic characteristics even though they have different driver mutations.
Certain dog breeds are also genetically predisposed to specific cancer types, suggesting strong genetic selection and gene-environment interactions. As an example, squamous cell carcinoma of the digit, a common nail bed tumor in dogs, occurs only in black poodles leaving light colored poodles almost entirely unaffected. Translational studies pinpointing specific genetic triggers in canine cancers can hence potentially reveal therapeutic and diagnostic biomarkers for aggressive human cancers. Matthew Breen, PhD, from NCSU’s college of veterinary medicine, cited the importance of creating more canine biobanks mapping the geographic distribution of dogs, such as the one by Canine Comparative Oncology and Genomics Consortium (CCOGC) and Pfizer. Among the many uses of such databases is to measure biological impact of environmental disasters, a process that takes decades in humans.
Dogs can also teach researchers new tricks to overcome limitations and define new uses for mammalian models. Ideas include patient-derived xenograft models for canine patients, cross-species clinical trials in dogs and humans, and repurposing of existing drugs in different cancers or as new agents for minimal residual disease. Participants said that addressing scientific, strategic and policy gaps in comparative oncology will guide rigorous preclinical testing and identify key biological pathways to reach go-vs-no-go decisions in drug trials faster. They highlighted the need for strong institutional support, training grants and shared resources, including clinical trial infrastructure and bioinformatics teams.
Mark Dewhirst, DVM, PhD, from DCI, emphasized bringing together veterinarians, material scientists, imaging experts, medical and radiation oncologists and getting them to communicate in a common language, a key requirement for collaborative multidisciplinary research. “It’s not trivial,” he said. “For example, we have taught mechanical engineers who study heat transport to understand the biology and applications of therapeutic hyperthermia in dog and human cancers.”
To learn more about the Consortium for Canine Comparative Canine Oncology, visit C3O.
Photos (in article): Megan Mendenhall, Duke Photography
Circle Photo (top): Jared Lazarus, Duke Photography