Canine cancer questions got $1.5 million closer to some answers last week when the AKC Canine Health Foundation and the Golden Retriever Foundation jointly awarded grants totaling that amount to two projects which will collaboratively research how lymphoma and hemangiosarcoma get started and spread in Golden Retrievers.
Lymphoma, cancer of the lymphatic system, strikes one in eight Golden Retrievers, and hemangiosarcoma, which attacks the lining of blood vessels to create tumors on the spleen, liver, heart and skin, affects one in 20, making the two diseases major health problems for the third most popular breed in the United States. Most dogs with lymphoma survive about a year after treatment, and with hemangiosarcoma, only four to six months even with aggressive treatment.
Although this research will be performed on a single breed, the CHF says the resulting information should help in early diagnosis and treatment of other breeds as well. In a CHF newsletter to its supporters, University of Minnesota’s oncology professor Jaime F. Modiano, V.M.D., Ph.D., was quoted as saying, “In the case of lymphomas, there are probably more than 20 subtypes of this condition, about six of which are commonly seen in dogs. As it turns out, the subtype of lymphoma tells us more about the disease and its behavior than the breed of origin. So, studying one type of lymphoma…makes the results more readily interpretable, and applicable, to many breeds.” Others who do genetic research in dogs support this concept.
The first three-year grant of just over $1 million brings together – again – Modiano, Matthew Breen, Ph.D., of North Carolina State University, and Kerstin Lindblad-Toh, Ph.D., of the Broad Institute of the Massachusetts Institute of Technology and Harvard University. The trio’s previous work together has revealed “several ground-breaking discoveries,” according to Shila Nordone, Ph.D., the CHF’s chief scientific officer. First, they identified several regions of the canine genome that contain genetic heritable, meaning they can be inherited, risk factors for both cancers. They also identified inherited changes in tumors that determine how long a dog will survive after treatment. The researchers determined that a “few heritable, genetic risk factors account for as much as 50 percent of the risk” for the two cancers.
Modiano, Breen and Lindblad-Toh believe their findings offer the potential to develop methods of assessing the cancer risks in individual dogs, as well as managing risk for all dogs. The risk factors and tumor changes point to pathways that define a cell’s ability to do what it does, Nordone explains. “When we look at results from the study of human cancer, we suspect there are problems in regulation of cellular function such as proliferation [the creation of new cells] and cell death.” Identifying which defects exist in the dog can help determine what treatments will be most effective in stopping those actions, which are key in cancer. “Cellular function is not static,” she says. “There’s an ‘on/off’ switch to everything. There’s growth, survival and death. In cancer, understanding what is defective will allow us to better diagnose, treat and even prevent cancer.”
The researchers will use the CHF-GRF funds to identify “precise mutations” for the heritable genetic risk factors and prove that they define the disease. “Their ultimate goal is to develop robust risk prediction tools, and hopefully, an accompanying DNA test,” according to the study description. The team will use a “large independent population of Golden Retrievers from the USA and from Europe” for its studies.
Jeffery N. Bryan, D.V.M., M.S., Ph.D., of the University of Missouri, Columbia, Anne Avery, V.D.M., Ph.D., of Colorado State University, and Heather Wilson-Robles, D.V.M., of Texas A&M University, are the recipients of the second CHF-GRF research grant of about $400,000.
For the next three years, they will identify novel proteins in the blood, and what happens upstream of a gene being turned on (known as “epigenetics”) to improve the diagnosis, classification and prognostication of B-cell lymphoma. About 70 percent of dogs with aggressive lymphoma have the B-cell subtype. To do this, the researchers will use state-of-the-art technology, allowing them to develop biomarkers for each class of lymphoma and to identify new therapy targets. The changes in front of and after the gene could serve as biomarkers of risk, allowing medicine or diet to prevent lymphoma in Golden Retrievers before it develops. Finally, the trio proposes to fully analyze lymphatic cancer stem cells from genetic changes on the inside to how it affects what a cell expresses on its surface. “If we understand where the dysfunction is at the individual cell level, then we can have an earlier chance of diagnosing the disease,” Nordone says. Such knowledge will allow diagnosticians to further identify which dogs would best benefit from which treatments.
By studying cancer from the perspective of protein and epigenetics together, “the discoveries made in each project can be combined, correlated and translated into biomarkers of risk, diagnosis and prognosis to advance the prevention and management of lymphoma in Golden Retrievers,” according to the study description.
Nordone says she loves all of these newly funded studies “because they’re collaborative in nature, and that really, really matters now. We’re pooling both physical and intellectual resources. That is huge.” Such collaborative research, she says is “absolutely the wave the future. I think we’re going to start to see collaboration at the forefront. We can’t work in isolation anymore.
“If you look at the strength of all these investigators, they come from very different backgrounds. They bring a lot to the table.” They are also from different universities, and “resources really do differ from place to place,” she says.
In addition, the CHF and GRF are “asking for deliverables,” Nordone says. “This is not science for science’s sake. This is science for the sake of doing something about the disease, for solving a problem. These are projects that are structured to translate to the patient.”
It has taken three years since the creation of the partnership between CHF and GRF to award these research grants. Studies considered for funding had to include at least three component projects and were reviewed by the “foremost experts in the field of veterinary oncology,” according to the CHF.
You can help support these projects by donating at www.support.caninehealthfoundation.org/cancer or www.goldenretrieverfoundation.org/Donatetoday.php. Dog clubs and organizations that wish to sponsor this research should contact firstname.lastname@example.org.