A dynamic collaboration between researchers in the veterinary college’s new Animal Cancer Care and Research Center and Virginia Tech’s Department of Biomedical Engineering and Mechanics has attracted substantial funding for a unique approach to treating osteosarcoma, a notoriously painful and aggressive bone cancer that primarily afflicts large-breed dogs, children, and adolescents.
Led by oncologic surgeon Joanne Tuohy, assistant professor in the Department of Small Animal Clinical Sciences, and biomedical engineer Eli Vlaisavljevich, assistant professor in the College of Engineering, the interdisciplinary team is working to refine a type of ultrasound technology, histotripsy, for the treatment of various canine cancers.
Typically requiring amputation of the affected limb and follow-up chemotherapy, treatment for osteosarcoma can be challenging for some pet owners, but the alternative — death due to tumor pain and metastasis — is far worse. And while treatment protocols and life expectancies haven’t meaningfully improved in several decades, Tuohy is encouraged that histotripsy has the potential to help both dogs and humans with osteosarcoma.
“Cancer clinical trials offer exciting opportunities to advance treatments,” Tuohy said. “But these trials require patience, coordination, and solid cooperation among researchers, clinicians, owners, referring veterinarians, and, of course, the patients themselves.”
One such patient is Balian, a 6-year-old Alaskan malamute that was diagnosed with osteosarcoma in February. Informed of the study by family friend Andrea Cangin ’98, Balian’s owner, Jake Polverini, was immediately on board. “Once we had accepted the fact that he was going to lose his leg,” Polverini said, “we wanted to help make sure a future dog wouldn’t lose a leg. No dog should have to go through this.”
Histotripsy, the technology used in the study, focuses ultrasound beams to non-invasively create cavitation bubble clouds, mechanically breaking down cells inside a defined area. The technique doesn’t use heat, an attribute that helps avoid damage to surrounding tissues.
“Even though this is what I do every day, I still think it sounds like sci-fi to be able to destroy tumors without making any incisions,” said Vlaisavljevich, whose lab explores a range of physical mechanisms through which ultrasound interacts with tissues in the body, including cancerous tumors.
When the ultrasound technology breaks apart the tumor cells, they release proteins, and the body’s immune system begins to recognize them as invaders. A strong enough immune response could even begin to recognize and attack metastatic growths or regrowth of the same tumor, which is highly desirable with an aggressively metastatic cancer like osteosarcoma that kills the majority of patients by its propensity to spread throughout the lungs.
Although histotripsy and related ultrasound-based immunotherapies are being developed for use in humans, there is little data on their use in dogs or on these types of tumors. As a result, Vlaisavljevich and Tuohy have designed a series of clinical studies that, if successful, will support the use of histotripsy as a treatment for canine osteosarcoma.
The team’s first study, conducted two years ago with local veterinarians and owners, tested histotripsy on the amputated limbs of tumor-bearing dogs. Because the researchers were not treating live patients — referred to as ex vivo, literally “outside a living body” — they were able to validate that the approach would be safe and would provoke the kind of immune response needed for success.
On the heels of the first study’s positive results, a grant from the American Kennel Club moved the study to the next phase — in vivo, or inside the bodies of dogs affected by osteosarcoma.
A case in point is Balian, whose amputation took place in early March. “He’s bouncing around, hopping through the yard like a champ,” said Polverini. “He still makes friends everywhere he goes.”
Although the ultimate goal is to avoid amputation entirely by offering the histotripsy treatment alone, Tuohy cautions that immunotherapy will likely be part of a multimodal approach, not a replacement for all other therapies. “If there’s one thing we’ve learned about cancer in the past half-century, it’s that we must be humble,” she said. “We don’t expect to find a silver bullet in cancer treatment with the technologies available.”
Vlaisavljevich, whose mother died of liver cancer when he was 4 years old, agrees. “Clinical research can be difficult,” he said, “and there are no sure things.” However, the incremental progress, the collaboration with a passionate interdisciplinary team, and especially the success stories of patients who have been helped by his research give him hope: “This is an extremely rewarding job. You’ve got to use setbacks to inspire you to keep going,” Vlaisavljevich said.
— Written by Mindy Quigley, clinical trials coordinator in the veterinary college’s Department of Small Animal Clinical Sciences.