Micrornas in the pathobiology of osteosarcoma

Osteosarcoma is the most common primary bone malignancy affecting children, adolescents and young adults. Around 30% of patients with localized osteosarcoma and 70% of patients with metastasis will experience treatment failure within 5 years of diagnosis. Such a dismal outcome has remained static for the past 20 years leading to an urgent need to identify novel targets and therapeutic agents that will improve patients overall survival and minimize immediate and long-term side effects of current chemotherapeutic agents. Additionally, osteosarcoma is commonly found in canines, with approximately 10,000 new cases each year in the US. The complex biology of osteosarcoma and tumor heterogeneity makes it very difficult to identify effective actionable targets and therapeutic agents. This chapter will highlight the recent developments in our basic understanding of microRNA mediated gene regulations in osteosarcoma and discuss the potential for development of microRNA-based prognostic biomarkers. Further, this chapter will analyze the recent development of preclinical evaluation of a novel agent Minnelide in the treatment of osteosarcoma and emphasize the prospects for combinatorial drug treatment in osteosarcoma.