With continued funding from a Terry Fox New Frontiers Program Project Grant (PPG), researchers at the University of British Columbia (UBC) have answered one of the biggest questions in the study of synovial sarcoma: where does this cancer begin?
In a new study published in Nature Communications, the team discovered that synovial sarcoma develops when a rare subset of fibroblasts become cancerous. By understanding where and how these tumours first form, the team can now begin identifying new ways to target and treat this devastating disease.
Closing a long-standing gap in cancer biology
Synovial sarcoma is a rare and aggressive soft tissue cancer that most often affects adolescents and young adults. These tumours have similarities to osteosarcoma, the cancer Terry Fox had; they are relatively rare, typically occur in the limbs of young people and spread aggressively. However, while cancer research has led to improved chemotherapy and survival for osteosarcoma, similar advances have not yet been achieved for synovial sarcoma. As a result, outcomes remain poor, with fewer than half of patients surviving ten years and only around a quarter surviving two years when the cancer has metastasized.
This disease also has unique biological features, including the presence of a hallmark oncogene called SS18::SSX – a fusion of two genes that disrupts normal cell behaviour.
To uncover the tumour’s starting point, the team created a mouse model expressing the same SS18::SSX fusion gene found in synovial sarcomas. With additional support from TFRI’s Marathon of Hope Cancer Centres Network, they validated the model using human tumour samples. When the fusion gene was introduced into mice, the animals developed synovial sarcomas that replicated human tumours 100 per cent of the time.
Using this model, the team applied advanced “omics” technologies to understand how SS18::SSX transforms healthy fibroblasts into tumours. Not only did they uncover how the fusion gene reprograms fibroblasts into a cancerous state, but they also discovered why synovial sarcomas are “immune cold,” making them difficult for the immune system to detect and attack.
This study also showed that SS18::SSX can push fibroblasts back into an early, embryonic state where they grow and divide rapidly, helping explain the cancer’s aggressive behaviour.
Turning discoveries into hope
Together, these findings shed light on key questions in the study of synovial sarcoma. With this validated model, the team is now actively exploring weaknesses within these tumours and testing new strategies to target them.
“This achievement was truly a team effort made possible by long-term support from the Terry Fox Research Institute,” says Dr. Michael Underhill, a professor at UBC and member of the PPG team.
“Now that we understand how synovial sarcoma starts, we have a path forward. Our goal is to turn that knowledge into more effective, personalized therapies that offer real hope to patients and families facing this cancer, and possibly other forms of cancer too.”
This study was funded by a Terry Fox New Frontiers Program Project Grant in New vistas on cancer biology and treatment: conceptual advancements from the forme fruste project. This project was renewed in 2025 to focus on improving outcomes for six types of sarcoma.