A story of cancer, canines and collaboration
RALEIGH, N.C.—With focus on the proverbial man’s best friend, researchers from the North Carolina State University College of Veterinary Medicine and its neighbor, the Lineberger Comprehensive Cancer Center, are combining their expertise to pinpoint the cause of non-Hodgkin lymphoma in humans and canines. The animal and human docs hope their collaborative effort leads to the identification of gene components resulting in more humane and earlier treatment.
The hope is that the canine can help his “best friend” understand how to diagnose and treat lymphoma.
The dog is an excellent model to study human cancer, particularly lymphoma, says Dr. Steven Suter, a veterinarian and NCSU professor of clinical sciences. The disease is biologically similar in human and canine patients.
Suter, Matthew Breen, professor of genomics, along with statistics professor, Alison Motsinger-Reif and Dahlia Nielsen, research assistant professor of genetics, represent the North Carolina college component.
Kristy Richards, geneticist and clinical oncologist, leads a team of researchers at the University of North Carolina Lineberger. The researchers are recruiting pet dogs diagnosed with lymphoma to collect tissue samples for study. The simple and speedy procedure at the NCSU Veterinary Teaching Hospital causes no discomfort to the dog, and owners receive $1,000 for their pet’s participation.
“There are very few places in the country where a top-rate veterinary program is in such proximity to a top-rate medical school with a comprehensive cancer center,” Richards says. “We aim to take full advantage of this partnership to discover, develop and test new treatments much faster than could be done in either organism alone.”
Labs from both institutions will study tissue samples from human and canine patients, targeted toward creating a genomic profile of non-Hodgkin lymphoma to give oncologists and veterinarians greater insight into the disease’s biology and improve their ability to diagnose the illness early.
“Canine lymphoma cells look similar microscopically and share similar staining for cell surface proteins commonly used for diagnosis,” Richards says. “These similarities make us hopeful that the remainder of the underlying biology, most importantly the pathways that lead to lymphoma development and progression, will be similar as well.”
Genomic profiling is only possible after the full genomic sequence of an organism is known, she says. The human genome sequence was published in 2001 and the canine genome sequence was published in 2005.
“We plan to look at all areas of the genome for changes in DNA copy number and RNA (gene) expression levels,” Richards says. “We’ll also be looking for particular DNA mutations that are specific to lymphomas and then see how much of this biology is shared between canine and human lymphomas.
Certain breeds such as boxers and golden retrievers are more predisposed to lymphoma than others, probably due to genetic predispositions concentrated in particular breeds during the selective breeding process, she says. Also, veterinary oncologists use similar chemotherapy regimens on dogs as humans, the same four-drug regimen (called CHOP) that human oncologists use.
“If we know how the canine lymphomas mimic human lymphomas, and we direct our new drug therapies to those proteins/pathways that are malfunctioning, we can gather information that will speed the development of the therapies for use in humans,” Richards says.
Statistics show more than 66,000 people each year are diagnosed with non-Hodgkin lymphoma, making it the fifth most common type of cancer. The most common subtype, which is also the most common subtype in dogs, is diffuse large B-cell lymphoma; affecting nearly 25,000 people per year—and about half of those people will die of their disease.
“Statistics on dogs are harder to compile of course, because not all owners take them to the vet, and even then, there are no national registries to keep track,” Richards says. “But it is estimated that 4 million dogs get cancer every year, and up to 25 percent of these are lymphomas, resulting in most of the affected dogs deaths.
“The goal is not to improve treatments for humans through the use of dogs at this point in the project,” says Suter. “The goal is to more thoroughly characterize canine B-cell lymphoma using a variety of molecular techniques to determine if the disease in dogs is similar to the human disease. Once this is definitively established, it will open the door to using dogs as a pre-clinical model to develop novel therapeutics for the human disease. Obviously, it will help dogs in the long run, also.”
Unlike chemotherapy, targeted therapy, such as the anti-CD20 monoclonal antibody Rituxan used in humans, is targeted for cancer cells specifically, he says. Therefore, learning what genes produce “bad” or cancer-promoting proteins, will allow the development of more specific and less toxic chemotherapies.
“The vast majority of cancer research over the last 30 to 40 years has been performed using mice and rats,” Suter says. “These are called xenograft studies, where human cancer cell lines are injected into rodents who have been genetically engineered to have a dysfunctional immune system so they don’t reject the human cells. So, the whole assay system is extremely artificial.
“These cancers in dogs are spontaneous, just like in people,” he says. “They are not induced in any way. So, all these factors make dog lymphoma a great model for human DLCBL and a variety of other cancers.”