Advances in osteosarcoma research: Pathogenesis and emerging therapeutic strategies

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, and continues to pose formidable clinical challenges due to its high invasiveness and propensity for early metastasis. Although recent advancements in multimodal treatment, such as neoadjuvant chemotherapy combined with limb-salvage surgery, have significantly improved local control, the 5-year survival rate for patients with metastatic or recurrent disease remains dismally low at 20-30%. In this review, we present a comprehensive synthesis of current knowledge regarding the molecular and genetic underpinnings of osteosarcoma pathogenesis. We highlight critical oncogenic mutations, dysregulated signaling pathways, and tumor microenvironmental factors that collectively drive tumor initiation, progression, and metastasis. Furthermore, we evaluate current therapeutic strategies and examine emerging approaches, including molecularly targeted therapies and immunotherapeutic modalities. These advance deepen our understanding of osteosarcoma biology, with implications for the development of more effective, personalized treatments.