One Health Research Is Advancing Canine Brain Tumor Knowledge
Dogs and people are susceptible to many of the same or very similar diseases. A type of brain tumor, meningioma, is an example. Both species are at risk for succumbing to the cancer’s debilitating, life-changing effects.
One Health research funded by the AKC Canine Health Foundation is supporting collaborative studies by investigators into human and canine diseases, who are searching for similarities in biological behavior and underlying mechanisms of this and other kindred diseases. Their synergistic insights and expertise are fast-forwarding progress in the therapeutic discovery pipeline.
Meningioma is the most common primary brain tumor in dogs, representing 50 percent of cases.1 Typically affecting senior dogs 10 years of age and older, meningioma develops in the meninges, the membranes that surround the brain, gradually compressing or squeezing brain tissue, nerves and vessels. Confusion, behavioral changes, seizures, and loss of balance are signs.
A four-year clinical trial is investigating a novel therapy for these challenging canine cases. Led by Timothy Fan, DVM, PhD, professor of veterinary clinical medicine and principal investigator of the Comparative Oncology Research Laboratory at the University of Illinois, the study is treating meningioma cases with a chemotherapy combination of procaspase-3 activator (PAC-1) and hydroxyurea.
PAC-1 and hydroxyurea are drugs that stimulate apoptosis, or natural cell death, within meningioma cells. While hydroxyurea alone has a modest effect on these tumors, the combination of the two drugs is thought to synergistically promote death of the cancer cells. Studies on cultured meningioma cells and tissues obtained from tumors from humans and dogs have supported the belief that the PAC-1 combination may be a useful chemotherapy drug for meningiomas in both species.
“This is the first study to validate a new therapy directly applicable to dogs with possible benefit to humans,” Dr. Fan says. “The hope is that the therapy, if effective, may potentially help humans with the most aggressive forms of malignant meningioma.”
The study is the inaugural clinical trial of the Comparative Brain Tumor Consortium (CBTC), a group founded in 2015 at a meeting at the National Institutes of Health (NIH). CBTC members are experts at veterinary school comparative oncology centers who participate in clinical trials designed by investigators at the National Cancer Institute’s Center for Cancer Research Comparative Oncology Program. The goal is to better understand naturally occurring canine brain tumors to advance outcomes for canine and human patients with brain cancer.
Amy LeBlanc, DVM, DACVIM, senior scientist and director of the Comparative Oncology Program at the National Cancer Institute, along with Andrew Miller, DVM, DACVP, assistant professor in anatomic pathology at Cornell University College of Veterinary Medicine, and Molly Church, VMD, PhD, assistant professor of pathobiology at the University of Pennsylvania School of Veterinary Medicine, are leading the investigation of the pathological process of canine meningioma. The work involves development of a grading and classification scheme for meningioma in dogs that will aid comparisons between human and canine tumor subtypes and comparative studies.
“We do not know if meningioma is inherited in dogs, but since it is common in some large breeds and mixed breeds, we suspect there are shared molecular pathways that contribute to the development of these tumors,” Dr. Miller says. “This study includes cases from many different dog breeds from around the country and will incorporate detailed clinical history, postsurgical outcome, histology, and immunochemistry of canine meningioma to hopefully provide more clarity regarding clinical outcome in affected dogs.”
“From this study, we aim to create a sound molecular classification for canine meningioma,” Dr. LeBlanc says. “Molecular changes that occur with this brain tumor are very important, as they can be used to identify novel biomarkers and predict prognosis.”
1LeBlanc AK, Mazcko C, Brown DE, et al. Creation of an NCI Comparative Brain Tumor Consortium: Informing the Translation of New Knowledge from Canine to Human Brain Tumor Patients. Neuro-Oncology. 2016;18(9):1209-1218.