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The role of targeted therapies in osteosarcoma is evolving as the field grows. Despite the success of cytotoxic chemotherapy and surgery as major components of the multimodal treatment approach for osteosarcoma, the disease is still one of the most common malignancies in children and young adults. Despite its favorable outcome, osteosarcoma is associated with frequent local and distant relapses, due to the selection of chemo-resistant clones of cells. The palliative use of intensive chemotherapy is an important component of the treatment of patients who relapse and are not candidates for surgery, radiotherapy, or second-line treatment. However, there is a pressing need for treatment approaches that can target the underlying causes of osteosarcoma, such as blocking the cellular events that drive neoplastic transformation and progression. In the last few years, several antiangiogenic agents have shown promising activity in preclinical models of osteosarcoma. However, the anticancer activity of these drugs has not translated into better outcomes for osteosarcoma patients. In this review, we highlight several areas of progress in targeting osteosarcoma via the use of bone-targeted agents, including bisphosphonates, antibodies, growth factors, and cells. The types of bone-targeted agents that are in clinical development, and their mechanisms of action, are discussed. The addition of these targeted agents to the multimodal treatment regimen is the subject of current clinical trials and may be the next generation of treatments
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