Collaborative Study Aims to Develop Cancer Risk Prevention Tools

Collaborative research, involving key canine cancer researchers, is focusing on developing markers to help diagnose and guide cancer treatment. A two-year, $1.06 million study, funded by the AKC Canine Health Foundation and the Golden Retriever Foundation, is based on newly discovered heritable and acquired mutations. Although the investigation primarily involves Golden Retrievers, a breed in which 20 percent of dogs die from hemangiosarcoma, the findings are expected to apply to all dog breeds. 

The researchers are Kerstin Lindblad-Toh, Ph.D., director of vertebrate genome biology at the Broad Institute of MIT and Harvard and professor at Uppsala University in Sweden; Jaime Modiano, V.M.D., Ph.D., the Perlman Endowed Chair in animal oncology at the College of Veterinary Medicine and Masonic Cancer Center of the University of Minnesota; and Matthew Breen, Ph.D., C.Biol., FSB, professor of genomics at North Carolina State Uni­versity College of Veterinary Medicine. 

The study stems from their recently completed research in Golden Retrievers, evaluating the relationship between inherited traits and susceptibility to hemangiosarcoma and lymphoma. Among their groundbreaking discoveries, the researchers identified several regions of the genome that contain heritable risk factors for these cancers. They also identified somatic mutations, alterations in DNA that happen after conception, in tumors that occur recurrently in both cancers. Some of these mutations appear to be linked to how long a dog with lymphoma stays in remission when treated with different types of chemotherapy. 

 “Our preliminary results indicate that a few heritable genetic risk factors account for as much as 50 percent of the risk for these cancers,” Lindblad-Toh says. “We can now look at the tumors in context of the inherited risk factors and start to understand how the tumor process starts. In the coming years, we will have a better understanding of how the mechanisms work and how the tumors continue to grow and spread based on these initial risk factors.” 

The current study has the potential to produce data that will lead to strategies for determining risk assessment in individual dogs. It also promises to provide insights on how to manage risk across the canine population as a whole. The researchers plan to validate genetic markers that can be used to determine risk in a large population of Golden Retrievers in the U.S. and Europe. Their goal is to develop robust risk population tools, including a DNA test, to detect dogs susceptible to cancer. 

Among the at-risk breeds for hemangiosarcoma are Bernese Mountain Dogs, Boxers, Flat-Coated Retrievers, German Shepherd Dogs, Portuguese Water Dogs, and Skye Terriers. The cancer, which comprises 5 to 7 percent of all canine cancers, is called a silent killer because it seldom is detected before the tumor ruptures, causing a life-threatening condition.  

Hemangiosarcoma typically starts in the thin layer of cells that line the interior of blood vessels. This intimate access into the blood supply contributes to the cancer’s metastasis throughout the body. Tumors in about 50 percent of cases start in the spleen. Other internal organs that are commonly affected include the heart, liver, lungs, kidneys, mouth, muscle, bone, brain, and bladder. Unlike these visceral hemangiosarcomas, tumors that occur in or under the skin typically show less aggressive behavior. 

In order to feed their growth, hemangiosarcomas use a process called angiogenesis to create new blood vessels from existing blood vessels. Unlike normal angiogenesis, which is well organized, tumor angiogenesis is disorganized and leads to formation of blood clots as well as hemorrhaging. Mini-hemorrhages within a hemangiosarcoma can heal quickly with dogs showing only mild signs, but severe hemorrhaging from a within a tumor can be fatal. 

Since signs of hemangiosarcoma are not apparent until the cancer is in advanced stages, it is virtually impossible to detect early. There are no reliable blood tests or imaging technology to identify the presence of this cancer before it is visible or has caused clinical signs. 

Without treatment, dogs with visceral hemangiosarcoma usually die in one to two weeks. The standard of care for hemangiosarcoma is surgery and/or chemotherapy, depending on several factors, such as the location of the tumor. Treatment principally is meant to prevent fatal blood loss and to extend life but is seldom curative. In tumors confined to the spleen, about 50 percent of treated dogs live four to six months after diagnosis. Only 10 to 15 percent survive 12 months or longer. The outcome is less favorable for dogs with tumors that originate in other organs and for dogs that have detectable metastasis at the time of diagnosis. 

If the research is successful, owners and veterinarians will be able to follow susceptible dogs and hopefully intervene before life-threatening signs appear. “Identifying the genetic basis of hemanigosarcoma will allow us to better understand the biology of this cancer,” Modiano says. “This may lead to preventive measures and effective new treatments.”  

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