Research status and prospects of molecular pathological mechanisms and novel therapeutic targets of osteosarcoma: a systematic review

Background: The treatment of osteosarcoma, a highly aggressive primary malignant bone tumour, has long faced limitations due to chemotherapy resistance, tumour het-erogeneity, and an immunosuppressive microenvironment. Methods: A/ncRNA networks), and dysregulated pathways (PI3K/AKT, Wnt/β-catenin)-and evaluates derived therapeutic strategies. Results: Targeted therapies demonstrate potential to improve prognosis in clinical trials; immunotherapies significantly enhance response rates by remodelling the cold tumour microenvironment; advanced technologies like nanotechnology and 3D-printed scaffolds over-come limitations of conventional treatments and enable integrated diagnosis and therapy. However, tumour evolutionary heterogeneity, off-target toxicity of targeted therapies, and translational gaps between animal models and clinical efficacy remain major challenges. Conclusions: Future directions require integrating AI-driven imaging omics, spatiotemporal multi-omics, and mechanically adaptive biomaterials to establish a precision management system. This will advance osteosarcoma therapy from survival prolongation toward functional cure-defined as complete tumour eradication with physiological reconstruction of bone structure/function (e.g., restoring load-bearing/joint mobility), while preventing treatment-related disability, ultimately achieving oncologic cure with preserved quality of life.