More than 10,000 cases of canine osteosarcoma are diagnosed in the United States every year. A team led by Amy K. Leblanc, D.V.M., Senior Scientist in the Molecular Imaging Branch, has discovered new molecular signatures that can predict clinical outcomes of osteosarcoma in both dogs and humans. Image credit: iStock
Scientists have identified patterns of gene activity that predict clinical outcomes for patients with osteosarcoma, an aggressive bone cancer. These molecular signatures are associated with prognoses for both humans and dogs, according to research led by Amy K. LeBlanc, D.V.M., Senior Scientist in the Molecular Imaging Branch.
The findings, reported August 17, 2023, in Communications Biology, are evidence of key similarities in the molecular makeup and clinical behavior of human and canine osteosarcoma — and hint at potential strategies for developing better treatment options for both species.
Osteosarcoma is diagnosed in fewer than 1,000 people a year in the United States. The small patient population limits opportunities to study the disease and investigate potential new therapies for this rare childhood cancer. In contrast, more than 10,000 cases of canine osteosarcoma are diagnosed in the United States every year. “This is an incredibly common and devastating medical problem for the veterinary community,” LeBlanc says.
Clinical trials for canine patients, supported by NCI’s Comparative Oncology Program, seek to identify better treatments for dogs with osteosarcoma, as well as deepen understanding of the disease to inform human studies. LeBlanc and her team turned to data from one of these canine trials to investigate whether molecular features could be used to identify subgroups of canine osteosarcoma.
Led by postdoctoral fellow Joshua Mannheimer, Ph.D., the team analyzed patterns of gene activity in tumor samples from nearly 200 dogs enrolled in a clinical trial. They compared these patterns to dogs’ survival times following their osteosarcoma diagnoses, as well as how long the animals remained disease-free following treatment. Within this data, the researchers found a molecular signature indicative of dogs’ clinical outcomes. They also confirmed that two previously identified signatures were associated with clinical outcomes for the dogs represented in their dataset. “The gene signatures that we applied clearly defined two groups of dogs: a group of dogs that does well, and a group of dogs that doesn't do as well,” LeBlanc explains.
They found that the same molecular signatures could also predict clinical outcomes when applied to data from human patients who had been treated for osteosarcoma. “This is the first time that anyone has shown that data that was derived from dog tumors has predictive capacity for people,” LeBlanc says.
LeBlanc says the composition of the signatures provides important clues into biological factors that influence osteosarcoma outcomes. Many of the genes that comprise the signatures are involved in interactions between tumors and immune cells, suggesting that patients with osteosarcoma fare better when their immune systems mount a robust anti-tumor response. This knowledge will help researchers investigate why many patients lack a strong immune response to osteosarcoma and how that response might be improved.