Investigating a new way to fight an aggressive cancer in dogs

Hemangiosarcoma is a common and aggressive type of cancer in dogs that arises from blood vessel cells and spreads very quickly, throughout the body, frequently affecting the spleen, liver, heart and muscles, among other organs.

"Because this type of cancer comes from blood vessels, it is common for these tumors to suddenly cause massive bleeding into the abdomen or chest," says Heather Gardner, D.V.M., Ph.D., DACVIM (Oncology), GBS20.

"Often when a dog is diagnosed, it is an emergency due to the blood loss associated with tumor rupture. They can have other problems related to hemangiosarcoma, such as lethargy, weakness, and shortness of breath. It's very frustrating for us clinically because it is so difficult to detect before it has spread."

Hemangiosarcoma can appear in almost any breed although golden retrievers are known to be highly predisposed, and the tumors usually arise in many different organs. Gardner, an assistant professor at Cummings School of Veterinary Medicine at Tufts University, says that once the cancer is diagnosed, typically it has already spread elsewhere in the body at a microscopic level, such as within the abdomen or to the lungs. Patients often develop disease progression despite immediate and aggressive therapy that includes both surgery and chemotherapy.

Gardner is a veterinary oncologist who has investigated cancers, such as osteosarcoma and lymphoma, in dogs for several years. With hemangiosarcoma, most veterinarians rely on clinical changes or imaging to monitor the disease. But with her osteosarcoma research, Gardner is studying ways to use a new technique called liquid biopsy to identify tumor specific markers in a blood sample, as a way to detect and monitor cancer. Now, she's applying that technique to hemangiosarcoma.

"Cells in the body, whether normal or cancerous, release tiny little snippets of DNA into the bloodstream," explains Gardner.

"Researchers know that the cancer cells have mutations in certain genes that you don't see in normal cells. We are using this to try and identify whether DNA is being released into the bloodstream from cancer cells and to accurately detect the presence of small amounts of cancer in patients that may be at risk of the cancer or in patients receiving treatment before a clinical relapse."

In addition to doing this research for the benefit of dogs, Gardner is also hoping that much of the knowledge learned can be applied to help improve liquid biopsy tests for people with a similar cancer called angiosarcoma. Because angiosarcoma is a rare cancer, with only 800 cases per year compared to over 50,000 cases per year of hemangiosarcoma in dogs, it is much harder to perform clinical trials.

The dog studies can help to optimize and validate a liquid biopsy platform to reduce the likelihood of failure once it transitions to human studies.

This work is part of a larger project led by Cheryl London, D.V.M., Ph.D., DACVIM, associate dean for research and graduate education at Cummings School. London is a veterinary oncologist/immunologist and the principal investigator on an RC2:High Impact, Interdisciplinary Science grant, which is associated with a parent UM1 Clinical and Translational Science Award to Tufts from the National Institutes of Health. Gardner, as well as veterinary nutritionist Lisa Freeman, D.V.M., Ph.D., DACVIM, and veterinary cardiologist Vicky Yang, D.V.M., Ph.D., DACVIM, are co-investigators.

Their goal is to leverage clinical trials in pet dogs to optimize early detection of both cancer and heart disease, and then translate these advances into human health.

Early steps in early detection

At the Comparative Pathology and Genomics Shared Resource, Gardner and London are designing a panel of genes that they know are commonly altered and mutated in hemangiosarcoma.

Their goal is to study plasma (blood) samples from dogs that have hemangiosarcoma and validate that the liquid biopsy approach can identify biomarkers or genes that are prognostic for patients. The second part of the project is to use those panels to determine which therapy is best for an individual dogs with hemangiosarcoma.

"The idea is that if a dog has a mutation in gene X, if we have a drug that treats a mutated gene X, then we should prioritize that therapy for that individual patient," says Gardner. "Based on prior studies we recently completed, we believe a few treatment combinations are going to have activity in this disease, and we want to assign those treatments based on the genetic changes we're seeing in our liquid biopsy tests to help improve outcomes."

Using the Clinical Research Shared Resource, Gardner and London plan to validate their custom canine panel for the liquid biopsy with existing biobanked plasma samples. Later this year, they'll enroll dogs in a clinical trial to help them design a rapid digital test that they can use to help clinicians make treatment decisions for patients.

"This time around, we're trying to answer very specific and challenging questions with the liquid biopsy technique. We have continuously been working to find ways to improve it in a translational way that not only benefits our patients, but hopefully can provide information to optimize approaches for a variety of cancers in people, as well," Gardner says.

Provided by Tufts University