They’ve served as guards, guides, and loyal companions. Now, dogs may assist researchers who hope to assess new cancer-fighting strategies. These strategies, which are meant to benefit both dogs and humans, involve personalized medicine—the identification of specific drugs to treat individuals based on their specific genetic or molecular makeup. To date, progress in personalized medicine has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Here’s where dogs can help.
While there are, relatively, many genetic differences among humans with the same type of cancer, there are far fewer genetic differences among dogs of the same breed, making it vastly easier to identify and study the genes driving canine cancers. Also, in pet dogs, naturally occurring cancers are heterogeneous, presenting an opportunity to answer questions about personalized medicine strategies and optimize their translation to human patients.
Recruiting dogs to fight cancer is part of an approach called comparative oncology. Of late, it has received a boost from the Comparative Oncology Program, which is run by the NIH and the National Cancer Institute (NCI). In fact, this program, through the Comparative Oncology Trials Consortium (COTC), in collaboration with the Translational Genomics Research Institute (TGen), has just completed a proof-of-concept study. It has determined that accomplishing tumor collection, prospective molecular profiling, and personalized medicine report generation within one week was feasible for dogs.
The one-week turnaround time for sample analysis is significant. It fits "a relevant clinical window for future comparative oncology trials to model human PMed advancements," said William Hendricks, Ph.D., a TGen staff scientist and an author of the study. “Future comparative oncology studies, optimizing the delivery of personalized medicine strategies, may aid cancer drug development.”
The COTC/TGen study’s results appeared March 17 in PLOS ONE, in an article entitled “Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials.” According to this study, the heterogeneity and complexity of cancer in the pet dog population and within cohorts of dogs with the same histological diagnoses is "well suited for modeling personalized medicine."
The study reported that 31 dogs with cancers of varying histologies were enrolled: “Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days).”
“Our canine companions are not only ‘Man’s Best Friend,’ but our study shows that dogs also can help human patients pursue battles against various types of cancer,” said Jeffrey Trent, Ph.D. TGen president and research director and the study’s senior author. “Not only do dogs with cancer benefit from this research, but people do, as well.”
The study summarized some of the advantages of using dog models:
Strong cancer breed predilections support "breed-based" germ-line discoveries that may streamline the definition of specific cancer targets as "drivers" of a cancer event.
Since comparative oncology modeling does not require up-front treatment with specific cancer treatment regimens, novel therapeutic agents can be offered through clinical trials at any stage in cancer presentation.
Compressed disease progression times in pet dogs with cancer allow for the evaluation of a variety of PMed interventions against longitudinal endpoints of cancer progression in ways not possible in the human clinic.
Finally comparative oncology randomized control trials can be conducted in the newly diagnosed, adjuvant (that is, minimal residual disease) and metastatic settings, evaluating the utility of PMed drug selection and algorithm prediction across a range of clinical scenarios.
The study was organized according to the propensity of different breeds to develop particular types of cancer. The study included Scottish terriers with bladder transitional cell carcinoma, golden retrievers with lymphoma, American cocker spaniels with melanoma, and a fourth group of dogs open to all cancer types.
The study, as part of the COTC effort, may help improve the design and execution of clinical trials in dogs with cancer. It may also contribute to the COTC’s ultimate goal: answering biological questions geared to inform the development path of these agents for future use in human cancer patients. According to the COTC, its trials "are pharmacokinetically and pharmacodynamically rich with the product of this work directly integrated into the design of current human Phase I and II clinical trials.”