Osteosarcoma (OS) is the most common non-hematologic malignant tumor of bone in adults and children. As
sarcomas are more common in adolescents and young adults than most other forms of cancer, there are a significant number
of years of life lost secondary to these malignancies. OS is associated with a poor prognosis secondary to a high grade
at presentation, resistance to chemotherapy and a propensity to metastasize to the lungs. Current OS management involves
both chemotherapy and surgery. The incorporation of cytotoxic chemotherapy into therapeutic regimens escalated cure
rates from <20% to current levels of 65-75%. Furthermore, limb-salvage surgery is now offered to the majority of OS patients.
Despite advances in chemotherapy and surgical techniques over the past three decades, there has been stagnation in
patient survival outcome improvement, especially in patients with metastatic OS. Thus, there is a critical need to identify
novel and directed therapy for OS. Several Phase I trials for sarcoma therapies currently ongoing or recently completed
have shown objective responses in OS. Novel drug delivery mechanisms are currently under phase II and III clinical trials.
Furthermore, there is an abundance of preclinical research which holds great promise in the development of future OSdirected
therapeutics. Our continuously improving knowledge of the molecular and cell-signaling pathways involved in
OS will translate into more effective therapies for OS and ultimately improved patient survival. The present review will
provide an overview of current therapies, ongoing clinical trials and therapeutic targets under investigation for OS.
Keywords: Bisphosphonates, BMP, IGF, IGFBP5, limb-salvage, osteosarcoma, OS99.
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