In March 2016, Ollie, a therapy dog at Boston Children’s Hospital, paid a bedside visit to 7-year-old Carter Mock. The pug and the boy had something in common: Both had lost limbs to the bone cancer osteosarcoma. Ollie’s left front leg had been amputated at the shoulder, while Carter had just had a new knee fashioned from his ankle in a procedure called rotationplasty.
Biologically, the osteosarcoma that dogs develop is remarkably similar to osteosarcoma in children and youths. The tumors develop primarily in the long bones, and the spread of tumor cells to the lungs represents the most significant threat and challenge. Similar chemotherapy agents are used in both dogs and human patients to kill residual cancer cells. Researchers are now mining these similarities in a quest for new treatments to benefit pets and people alike.
Comparing canine and human osteosarcoma
The cure rate for pediatric osteosarcoma has been stuck at 60 to 70 percent for more than three decades, unlike some other childhood cancers, such as acute lymphoblastic leukemia that today enjoy cure rates hovering around 90 percent. The prognosis in dogs with osteosarcoma is dire: Only about 10 percent survive, and most succumb within two years of diagnosis.
In their current project, Katherine Janeway, MD, a pediatric oncologist at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and veterinary oncologist Cheryl London, DVM, PhD, of Tufts Medical Center and Cummings School of Veterinary Medicine at Tufts University, are comparing the genetic abnormalities in tumor samples from dogs and human patients. As they uncover common pathways, they plan to develop clinical trials of immunotherapy, using novel agents that stimulate the immune system to try to kill cancer cells in dogs.
After analyzing the results, the most promising approaches will be moved into clinical trials for children. With well over 10,000 dogs diagnosed with osteosarcoma every year, compared with 1,000 children and youth, there’s an opportunity to glean information from canine trials relatively quickly.
“For designing clinical trials for osteosarcoma,” Janeway says, “the data from dogs is incredibly valuable.”
Janeway and London’s research is part of an emerging interest in comparative oncology. In the summer of 2015, the National Academy of Medicine held a workshop on the subject attended by about 200 veterinarians, physicians and government and industry representatives to lay the groundwork for collaborative cancer studies. In late 2016, the National Cancer Institute issued a major call for proposals designed to “establish the suitability of canine models” to study human cancer therapies, particularly immunotherapy, one of the most dynamic areas of cancer research today.
“Dogs can offer proof of principle,” London says. “As helpful as mouse models are, dogs are much closer to humans. They spontaneously develop similar cancers. They also have intact immune systems that possess the same variability as human immune systems, which is lacking in most mouse models.”
Immunotherapy trials: helping dogs and humans
Researchers have long thought that the immune system can play a role in fighting osteosarcoma, Janeway says, leading to clinical trials of various immunotherapy approaches over the last two decades. She notes evidence that suggests that when children with osteosarcoma relapse, the disease may spread to the lungs because the immune system is not properly monitoring the lungs.
“Investigating the similarities in dog and human osteosarcoma and conducting clinical trials in dogs with osteosarcoma will really help us design the best trials for children with this cancer,” Janeway says.
And, says London, “we will help dogs with osteosarcoma at the same time.”
The research was featured this week on CBS Sunday Morning:
Carter and Ollie
Carter, now 8, rotationplasty and prosthetic leg in place, is back to an adventurous life that includes aerial climbing and ice climbing.
“Few people know about osteosarcoma in children. They’re more aware of it in dogs,” says Danielle Mock, Carter’s mother. “Taking what we learn from the experience of canines to improve the care of children and adults with osteosarcoma is an amazing and hopeful idea.”
Ollie was diagnosed with osteosarcoma in 2014 after he fell in the kitchen of his owner’s suburban Boston home. Now he hops around on three legs. “If Ollie gets another tumor,” says his owner, Gail MacCallum, “I’d be happy to sign him up for this research.”