Can the study of cancer in dogs lead to new treatment options for humans? Scientists at the North Carolina State University College of Veterinary Medicine and the Duke Cancer Institute believe so and have entered into a collaboration designed to facilitate research projects aimed at benefiting both species. Established in 2015, the Consortium for Canine Comparative Oncology (C3O) funded its first four research studies last July, said Michael Kastan, M.D., Ph.D., executive director of the Duke Cancer Institute. The joint goal, he reported, is to establish a more formal investigational relationship between the two institutions, which previously had seen intermittent interactions between their faculties. “We decided that we could work together much more effectively than we could apart by studying tumors at the basic science level, at the drug development level and at the clinical level,” Kastan said of C3O. “As targets are identified and drugs are developed, we can test them in both patient populations, and that can save pharmaceutical companies a tremendous amount of time and money because clinical trials in the canine population can be done at a much lower cost. “Information learned from clinical trials in the canine population can then be used to better design the human clinical trials in terms of how to dose, schedule and combine drugs.” Cancer researchers working in the realms of physician-based and veterinary oncology have a long history of collaboration, said Michael W. Nolan, DVM, Ph.D., Dipl. ACVR, co-chairman of the C3O steering committee. “Individual collaborations are still the force propelling scientific gains,” said Dr. Nolan, assistant professor of radiation oncology at the NCSU veterinary college. “The C3O just provides structure to bring researchers together and support to get the work done.” Dogs a Better Model Dogs as a sentinel species in the study of cancer makes sense for many reasons: The American Veterinary Medical Association estimates that 50 percent of dogs are diagnosed with cancer in their lifetime and that 25 percent will die from it if they reach age 10. Canine cancer tends to grow much more quickly, which gives researchers a faster path of study. Many of the cancers found in dogs are found in humans, and the treatment modalities—primarily surgery, radiation and chemotherapy—are similar. “There are several examples where the clinical and biological features of canine and human cancers are so similar that we can learn a lot about one by studying the other,” Nolan said. “A great example is osteosarcoma. If you gave a pathologist slides of an osteosarcoma from both a child and a dog, they likely wouldn’t be able to tell you which slide came from which patient. “The common biology, combined with the fact that we frequently see this disease in the veterinary clinic, gives us a great opportunity to rapidly advance knowledge regarding a devastating pediatric tumor, whereas that progress would be slower without dogs simply because the disease is rare in children.” Perhaps most importantly, dogs share our environment, noted Matthew Breen, Ph.D., CBiol, FRSB, the Oscar J. Fletcher Distinguished Professor of Comparative Oncology Genetics at NCSU. Dogs breathe the same air we do, drink the same water, eat much of the same food and are exposed to the same potential environmental carcinogens, such as pesticides and herbicides. By contrast, laboratory mice—the primary model for decades—live in a sterile environment and are genetically engineered to develop tumors. As a result, they are not a very predictive model of what happens in a human setting. First Funded Studies A scientific review board has been established within C3O to evaluate and approve clinical studies to receive grants through the consortium. The board is led by Kastan and the NCSU veterinary school dean, Paul Lunn, BVSc, Ph.D., Dipl. ACVIM. These four studies have been approved for the first year: “A Phase 1 Clinical Trial of CP-DOX in Dogs: A Novel Nanoparticle Formation of an Old Drug,” for treating dogs with high-grade B-cell lymphoma. Led by NCSU associate veterinary professor Steven Suter, VMD, Ph.D., Dipl. ACVIM, and Duke biomedical engineer Ashutosh Chilkoti, Ph.D., the study will examine a modified molecule of adriamycin that targets tumors while sparing healthy tissue. “Development of a Personalized Medicine Pipeline for Treatment of Sarcomas,” to identify options for personalized sarcoma treatments in dogs and humans. Led by Breen and Duke orthopedic surgeon William Eward, DVM, M.D., the study will look at patient-derived xenografts from human and canine osteosarcomas and compare the mutational landscape of their DNA sequences. “A Cross Species Genomic Analysis of Osteosarcoma: Implications for Novel Therapeutic Approaches,” to identify molecular mechanisms of sarcomagenesis and determine therapeutic uses for drugs against mutation. Led by Breen and Dr. Eward, the study will sequence the coding region of the genes in human and canine osteosarcomas to identify similarities. “Identification of Carcinogen-Induced Mutational Signatures in Human and Canine Bladder Cancer,” to characterize a genetic signature of a carcinogen in cells and its appearance in tumors. Led by Breen and Duke surgical oncologist Brant Inman, M.D., MS, the study will examine whether environmental influences genetically affect people and dogs similarly. All the dogs involved in C3O-funded studies are client- owned pets, Dr. Suter said. “Many times the animals, similar to humans, are end-stage patients for whom we have run out of options,” he noted. “Their owners are folks who love their animals and are trying to help their pets as well as others with a similar form of cancer.” Trickle-Down Research These and future studies funded by C3O grants promise significant advancements in the treatment of cancer in humans, but the value to canine patients also is great. Inevitably, the researchers said, what once was available only through veterinary oncology specialists will be available to general practitioners. “As we develop new compounds for the treatment of canine cancer, these compounds will eventually be approved for use in the general canine population and could be delivered in the private-practice setting,” Kastan said. “If the only place to deliver these therapeutics was the high-tech veterinary schools, then we haven’t made a maximal impact. The goal would be that this eventually will be the way we treat canine cancers.” Could the work facilitated by C3O benefit animal species besides dogs? Nolan thinks so. “The C3O acronym has the word canine in it, but this doesn’t need to be dog-centric, and in some circumstances it probably shouldn’t be,” he said. “For example, feline oral squamous cell carcinoma is an interesting model of HPV-negative head and neck cancer. “And it doesn’t have to stop with dogs and cats,” Nolan added. “There are plenty of species that develop cancer, where we can perform studies that have dual benefit to veterinary and human cancer patients.” Breen agreed. As part of a broader study, his laboratory investigates cancers in a number of species, including cats, wolves, sea lions, polar bears, elephants and even hedgehogs. “Cancer affects all animals,” he said, “and by studying multiple species with shared cancers, we have a greater opportunity to determine what drives these diseases and how to combat them.” Learn More The Consortium for Canine Comparative Oncology held its inaugural symposium last March. More than a dozen presentations were recorded and are available for viewing at their website. Originally published in the October 2016 issue of Veterinary Practice News. Did you enjoy this article? Then subscribe today!
