Canine patients hold key to new bone cancer therapies for dogs and people

A research team led by Dr. Behzad Toosi of the Western College of Veterinary Medicine (WCVM) is focusing on the characteristics of osteosarcoma that are common to both species. This relatively new approach to studying cancer is known as comparative oncology, and it promises to significantly speed up the development of new treatments for both dogs and people.

Comparative oncology seeks to bridge the gaps between laboratory research and human clinical trials by combining research from other fields such as veterinary medicine.

 “[Dogs] share a household with you and they develop the same kinds of cancers as you, and those cancers are very, very similar genetically or molecularly,” explains Evelyn Harris, a graduate student and member of Toosi’s research team.

“It’s interesting to study comparative oncology because it is a stepping-stone between the mouse model and the human model.”

The researchers’ recent focus has been on small proteins called receptors that are found on the surface of cells. Although these receptors provide many essential functions to cells in the body, they’re also known to be easily “hijacked” by cancer cells and used for their benefit.

But if researchers could use these receptors to specifically target cancer cells and deliver treatments more effectively, their use could ultimately reduce the side effects of widespread chemotherapy drugs.

In osteosarcoma the small molecules of interest are erythropoietin-producing hepatocellular (Eph) receptors. Although they’re found on most cells in the body, previous research indicates that some subtypes of these receptors are overabundant in many types of human cancers.

“These [receptors] are emerging as some molecules that are very important in regulation of invasiveness of different cancers in humans, but they haven’t been studied in dogs,” says Toosi, an assistant professor in the WCVM’s Department of Small Animal Clinical Sciences. He also holds the college’s Allard Research Chair in Oncology.

After exploring these receptors to determine their role in the progression of dog cancers, Toosi and his research team have successfully demonstrated the overabundance of some receptor subtypes in osteosarcoma cancer cells from dogs.

Further investigations of some Eph receptor subtypes revealed that they play an essential role in osteosarcoma by enabling cancer cells to grow and move faster — ultimately contributing to the cancer’s aggressiveness.

Since there have already been some attempts to target these receptors in human cancers, Toosi is optimistic that it’s possible to target and interfere with these receptors as a means of more effectively treating osteosarcoma in dogs.

“These receptors are very promising for dog malignancies,” says Toosi. “They could lead to new clinical interventions for treatment of dog osteosarcoma.”

Traditionally, cancer therapy for dogs with osteosarcoma involves more invasive treatments such as radiation and chemotherapy — treatments with side effects that often trump those caused by the cancer.

“A lot of people will amputate the limb to get rid of the primary bone tumour and then only get a few more months with the pet,” says WCVM graduate student Dr. Jessica Sharpe, another member of Toosi’s research team.

Sharpe worked in private practice as a small animal veterinarian before transitioning into research. After seeing several cases of osteosarcoma each month in her practice and witnessing the devastating effects of the disease on pets and their families, she emphasizes the need to develop new treatment methods.

Comparative oncology may be the key to developing these new treatments more quickly — and that’s a promising advancement for both humans and their furry friends.

Dogs have a much shorter lifespan than humans, and they develop osteosarcoma naturally and at a higher rate than humans. As a result, new treatments can be taken to clinical trials sooner than is possible in their human counterparts.

“Since the biology of cancer is similar between dogs and humans, these investigations in dog clinical trials can inform further research or clinical trials conducted in humans,” says Toosi.

Maya Kliewer of Saskatoon, Sask., is a third-year veterinary student at the Western College of Veterinary Medicine (WCVM) who worked as a summer research student in 2021. Her story is part of a series of articles written by WCVM summer research students.