ENGINEERING COMPLEX BONE TUMOUR MODELS: UNRAVELLING TUMOUR MICROENVIRONMENT FOR DRUG DISCOVERY

Osteosarcoma, a highly aggressive bone cancer primarily affecting children, adolescents, and young adults, remains one of the most challenging paediatric cancers to treat. Despite advances in cancer research, the standard-of-care treatment for osteosarcoma has remained largely unchanged for nearly 50 years. The prognosis for patients with secondary lung metastasis is particularly poor, with approximately 70% succumbing to the disease within three years. Compounding this issue, osteosarcoma's rarity significantly limits the recruitment of eligible participants for clinical trials, further delaying the development of effective treatments. Traditional 2D cell cultures have long been the primary in vitro model used in cancer research. While these models are cost-effective and relatively straightforward to produce and maintain, they fall short in replicating the solid tumour characteristics and complex interactions between tumour cells and their surrounding microenvironment. This disconnect has contributed to the high failure rate of preclinical drug candidates in clinical settings, emphasizing the urgent need for more representative in vitro models. Emerging research has highlighted the potential of advanced 3D models in bridging this gap. These models more accurately mimic the phenotypic behaviour of primary tumours, particularly in sarcomas like osteosarcoma, where growth rates, cell morphology, cell-cell junctions, and kinase activation in spheroids exhibit remarkable similarity to their in vivo counterparts. Developing such models has become essential for unravelling the complexities of osteosarcoma progression and identifying novel therapeutic targets. This presentation will explore the innovative osteosarcoma models developed in our laboratory to address these challenges. By recreating the intricate interplay between osteosarcoma cells and key components of the tumour microenvironment, our models aim to provide deeper insights into disease mechanisms and progression. Additionally, we will discuss how these models are being utilized to evaluate and accelerate the development of novel therapeutic strategies, with the ultimate goal of improving outcomes for patients facing this devastating disease. Through this work, we aim to contribute to a paradigm shift in osteosarcoma research, highlighting the critical role of advanced in vitro models in overcoming longstanding barriers in translational cancer research.