Researchers at the University of Florida College of Veterinary Medicine and the UF Health Cancer Center have identified a crucial link between a gene mutation and immune system signaling in canine hemangiosarcoma, a discovery that could lead to better treatments for both dogs and humans with similar cancers.
The research focuses on hemangiosarcoma, an aggressive cancer that forms malignant blood vessels in dogs. This life-threatening condition is difficult to diagnose early, as tumors can grow silently before rupturing without warning, leading to emergencies. The prognosis is poor, with only 10% of diagnosed dogs surviving beyond one year, and none living past two years.
While hemangiosarcoma can affect any breed at any age, older golden retrievers are especially susceptible. The cancer’s high incidence in dogs — estimated at more than 50,000 cases annually in veterinary clinics — provides researchers with valuable data that could benefit human patients with angiosarcoma, a rare but similar cancer that affects about 1,000 Americans each year.
“The best four-legged friends of humans help us do high-quality cancer research,” said Jon Kim, D.V.M., Ph.D., an assistant professor at the college and the study’s lead researcher. “We learn a lot about human cancer biology from studying cancer in dogs.”
The research team’s findings, detailed last year in two pioneering publications, most recently Cancer Gene Therapy, reveal an important discovery about how this cancer grows and spreads. The team found that hemangiosarcoma doesn’t just create its own blood vessels — it hijacks healthy cells nearby, forcing them to help build the blood vessels that feed the tumor.
Even more significantly, the researchers discovered that a specific genetic mutation in the PIK3CA gene causes cancer cells to send out signals that confuse the body’s immune system.
While scientists have known about PIK3CA mutations in human cancers for years, they haven’t fully understood how these mutations affect the way cancer grows and responds to treatment. The study findings help fill in these knowledge gaps, Kim said.
“This new research provides us with critical insights that could lead to novel therapies for both canine hemangiosarcoma patients with this mutation and human patients with angiosarcoma,” he said.
The rarity of human angiosarcoma has hampered research efforts, making it difficult to gather enough data for meaningful clinical trials and to understand the cancer’s fundamental biology. However, the much higher incidence of hemangiosarcoma in dogs offers researchers a robust natural model for study, the researchers said.
“We see a lot of dogs with hemangiosarcoma in veterinary clinics,” Kim said. “We hope our work will be beneficial, not only for sick dogs, but also for human patients with this terrible disease.”
In laboratory experiments, the research team discovered that hemangiosarcoma cells have a unique ability to stimulate blood cell production. This process could influence the generation of ‘cancer-friendly’ immune cells, effectively confusing the body's immune system and enabling cancer growth. The team's recent work shows this process can be driven by the mutant PIK3CA gene, suggesting new therapeutic possibilities targeting this mutation and its effects on immune disruption.
“Our hope is that this innovative approach will help us better understand the clinical and translational significance of our findings from dogs for rare human cancers,” Kim said.
Journal
Cancer Gene Therapy
Article Title
PIK3CA mutation fortifies molecular determinants for immune signaling in vascular cancers
Article Publication Date
21-Dec-2024