Interrogating Functional Dependencies in Paediatric and Adolescent Osteosarcoma

Osteosarcoma (OS) is a primary malignant tumour of the bone, mainly affecting teenagers and young adults. Despite multimodal treatments, cure rates for patients with metastatic or relapsed disease are poor. In this thesis I aimed to identify targetable pathway dependencies in osteosarcoma using a functional genomics approach. We have identified 17 therapeutically sensitive molecular targets. Moreover, we demonstrate that the efficacy of vinblastine to inhibit tumour growth and significantly extend survival in vivo. The finding of this thesis provides foundational evidence to suggest underlying mechanisms of osteosarcoma tumorigenesis, proposing multiple targeted therapeutic approaches and treatment combinations with potential to impact osteosarcoma patient outcomes.