Rottweilers & Hemangiosarcoma Research: Q & A with Dr. Modiano
Most Rottweiler owners will agree no canine cancer is as scary as hemangiosarcoma (HSA). Challenging to diagnose and equally difficult to treat, HSA often renders a one-punch knockout when a tumor ruptures causing dogs to bleed to death internally.
Promising research at the University of Minnesota is gaining a heavy-weight advantage over this devastating cancer. The work represents more than two decades of investigations. A combination diagnostic and treatment strategy offers a unique approach. The Shine On Suspicion (SOS) blood test identifies features of rare cells in the blood linked to this insidious cancer, allowing for potentially earlier treatment. Dogs that are thought to be at high risk for HSA via findings from the SOS test may then be able to receive a novel targeted toxin therapy called eBAT, developed at the University of Minnesota, which may extend their lives.
Bear in mind that although the SOS blood test and eBAT are gaining favor in clinical trials, both are months to years from being widely available in veterinary clinics. “We hope to move the SOS blood test to the real world soon, so dogs can be tested through their veterinarian,” says Jaime F. Modiano, VMD, PhD, the Perlman Endowed Chair in animal oncology at the University of Minnesota. “eBAT will remain experimental until it is approved by the Food and Drug Administration as a treatment modality, and then additional work will be needed before it can be used for preventive purposes.”
The complexity of HSA is notable as reflected in the diversity of its manifestation in individual dogs. More than 50 percent of affected dogs die within four to six months, almost 90 percent within a year. A tumor ruptures causing acute, severe blood loss, collapse, shock, and sudden death in many cases. “This cancer has high metastatic propensity and is extremely drug-resistant, making it one of the most aggressive cancers seen in dogs,” Dr. Modiano says.
Although much is unknown about HSA, characteristics of the cancer define its idiosyncratic nature. “One of the most challenging things about HSA is that it grows silently and initially without clinical signs,” says Dr. Modiano. “The diagnosis is typically made when the cancer is in the advanced stages and hard to treat.”
More than 50,000 companion dogs in the U.S. are believed to develop HSA each year, estimates the University of Minnesota research team. Naturally, people who have lost dogs to this cancer seek ways to prevent it from occurring in other dogs. “There is no known effective preventive,” he says. “Altering lifestyle behaviors, reducing environmental concerns, or feeding special diets or supplements have no impact on the development of this cancer.”
HSA starts in bone marrow cells that help to form new blood vessels throughout the body, giving tumor cells access to multiple tissues. Tumors primarily occur in the spleen, followed by the heart, skin and liver. The HSA cells incite the formation of abnormal vessels where blood tends to pool and clot. Eventually these clots obstruct the vessels and prevent fresh blood and nutrients from reaching the tumor environment, causing cells to die. This cell death causes ruptures in the tumor, allowing blood to escape into the abdomen, heart sac, chest, or subcutaneous tissue, depending on the tumor location.
The goal of treatment is to slow down or delay the spread of disease — and importantly, to prevent a life-threatening bleeding episode. The standard of care is surgery to excise a tumor mass followed by chemotherapy.
The combination SOS blood test and eBAT treatment developed at the University of Minnesota are HSA game-changers. More than 40 features of rare cells in the blood of dogs diagnosed with HSA were used to develop the SOS blood test. Artificial intelligence is used to analyze a dog’s susceptibility to developing HSA based on these parameters.
eBAT, short for EGF-bispecific angiotoxin, delivers a lethal bacterial toxin payload to tumor cells by attacking two proteins, epidermal growth factor receptor (EGFR) and urokinase-type plasminogen activator receptor (uPAR), found on the cell surfaces of HSA tumors. The discovery that the proteins are expressed at the same time triggered the hypothesis that the tumors would be sensitive to a targeted therapy that attacks both simultaneously.
“After eBAT is injected into a vein, it enters tumors where it specifically kills malignant cancer cells that display EGFR and uPAR on their surface,” Dr. Modiano says. “Another unique property of eBAT is that it kills inflammatory cells and blood vessels in and near tumors, making the environment inhospitable for the cancer cells. Importantly, eBAT does not cause any severe side effects.”
The ongoing study will generate knowledge related to the accuracy of the SOS test to predict whether dogs will develop HSA, how long before tumors develop in dogs designated as high risk, whether low- and medium-risk dogs eventually develop tumors, and whether high-risk dogs treated with eBAT change status to low or medium risk.
“The concept is that the properties of the SOS blood test and eBAT set this combination apart. They not only predict if a dog is at high risk or perhaps has an incipient HSA, but also provide a way to reverse that and prevent the tumor from ever forming,” says Dr. Modiano.
While the SOS blood test and eBAT await approval for veterinary clinical use, the best advice for the owner of a dog suspected of having cancer is to see a specialist. “We recommend consulting and following the advice of a specialist,” Dr. Modiano says. “It is important to conform to best medical practices and not give in to practices that give false hope. Talk to your dog’s health care team to understand the results of tests and options available.”