Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases which is the main cause of death. Unfortunately, the conventional chemotherapy is not fully effective on osteosarcoma metastases. The progression of a primary tumor to metastasis requires multiple processes, which are neovascularization, proliferation, invasion, survival in the bloodstream, apoptosis resistance, arrest at a distant organ, and outgrowth in secondary sites. Consequently, recent studies have revealed new insights into the molecular mechanisms of metastasis development. The understanding of the mechanism of molecular alterations can provide the identification of novel therapeutic targets and/or prognostic markers for osteosarcoma treatment to improve the clinical outcome. 1. Introduction Osteosarcoma (OS) most often occurs, during childhood and adolescence, in the metaphysis of long bones, including large growth plates with high proliferation activity and bone turnover [1]. Historically, patients with primary OS have been treated with resection surgery alone, resulting in poor prognosis. Clinical outcome of localized OS has improved with neoadjuvant chemotherapies, based on methotrexate, cisplatin, doxorubicin, and ifosfamide treatments. The 5-year survival has indeed increased to around 60%. However, the 5-year survival of patients with OS metastasis still remains about 30% [2–7]. OS metastases appear most frequently in the lung [8] and are the main cause of death for patients with OS, because micrometastases are undetectable at initial diagnosis [9, 10]. Taken together, OS patients with metastases present further worse clinical results than those without metastases. Thus, more effective treatments and/or a more personalized therapy (i.e., treatments according to specific genes or protein profile expressions) are needed for patients with OS associated with pulmonary metastases. The establishment of cancer metastasis involves several complex steps: intravasation, survival in the circulation, arrest at a distant organ, extravasation, and growth in secondary sites (Figure 1). Molecular alterations of these steps have been practically analyzed. The understanding of metastasis mechanism might allow us to find new molecular targets for improvement of the patients’ survival. This paper describes the molecular factors associated with OS development and summarizes the main molecular alterations involved in this bone disease, especially in metastatic OS, which strongly contribute to the development of novel therapeutic approaches.
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