Next-Generation Therapies for Bone Cancer: Targeted Therapy, Immunotherapy, and Nanomedicine Innovations.

Bone cancer remains a challenging malignancy, with high mortality rates in advanced or metastatic stages. Recent therapeutic advances have increasingly focused on integrating targeted therapy, immunotherapy, and chemotherapy with nanodrug delivery systems (NDDS) to enhance treatment efficacy. Chemotherapy remains a cornerstone, with optimized regimens improving outcomes while reducing systemic toxicity. Immunotherapy (including checkpoint inhibitors, adoptive T-cell transfer, and CAR-T cell therapy) has demonstrated promising clinical potential. Targeted therapy disrupts key molecular pathways critical for tumor progression, offering a more selective approach with fewer adverse effects. NDDS amplify these strategies by improving drug bioavailability, enabling sustained and controlled release, enhancing tumor penetration, and overcoming drug resistance within the bone tumor microenvironment. They also facilitate the co-delivery of multiple agents for synergistic effects. This review provides a comprehensive analysis of the clinical applications of targeted therapy and immunotherapy in primary and secondary bone cancers, critically evaluates recent advances in NDDS, and highlights their transformative potential in precise drug targeting and multimodal regimens. By bridging established treatment modalities with emerging nanodelivery innovations, it offers an integrated framework to guide future translational research in bone cancer therapy.