Defining drivers of metastatic osteosarcoma

Osteosarcoma is the most prevalent primary bone tumour, with a predominance in children and adolescents in periods of rapid growth. Despite aggressive multimodal therapy including chemotherapy (methotrexate, doxorubicin and cisplatin) and surgery, the average 5-year survival for osteosarcoma is ~70%. Metastatic disease, most commonly to lung, is the leading cause of death for osteosarcoma patients. 20% of patients have detectable metastatic disease at diagnosis and >80% are assumed to have micro metastasis, 50% of which will progress. The 5-year survival for metastatic osteosarcoma is ~20% and represents a significant clinical challenge. Improvements in the understanding and treatment of metastatic osteosarcoma is the only way to improve patient survival. Here we will develop, characterize and then utilize clinically representative models of osteosarcoma metastasis to determine targetable pathways that drive tumour dissemination to the lung and other tissues. We will then test the efficacy of pharmacologically inhibiting these pathways to prevent metastatic disease.