Introduction: Advances in the treatment of osteosarcoma (OS) came in the mid-1970s, when adding chemotherapy to surgery significantly improved patient survival. OS outcomes have since plateaued, however, despite exhaustive clinical investigations.Area covered: This review focuses on the most significant recent results of trials (in phases II and III) on localized and metastatic/relapsing OS and offers an overview of new targeted drugs.Expert opinion: Recent findings confirm the MAP (methotrexate, doxorubicin, and cisplatin) regimen as the gold standard for OS patients, also in metastatic cases, and the inefficacy of augmenting or modifying chemotherapy in poor responder patients. Immunotherapy and several tyrosine kinase inhibitors seem to be effective and promising in the treatment of OS. Optimizing the use of active drugs available by personalizing chemotherapies might prove important in the future. We urgently need bench-to-bedside research on OS. This will need to involve the extensive sequencing and immunoprofiling of all resected tumor tissue to find new therapeutic agents, especially for relapsing/metastatic patients. The low incidence of OS, its genomic complexity, and differences within and between tumors combine to complicate efforts to elucidate the biology of this disease. This means that we need to pool the resources of different groups studying OS and support translational research.
Keywords: Doxorubicin; cisplatin; etoposide; high-dose methotrexate; ifosfamide; mifamurtide; osteosarcoma; targeted therapy.