Iron-Related Metabolic Targets in the Treatment of Osteosarcoma: Research Progress and Prospects

Iron metabolism has emerged as a critical regulator of cancer biology, with mounting evi-dence linking iron dysregulation to tumor initiation, progression, and resistance mecha-nisms. In osteosarcoma (OS), the most common primary bone malignancy and a leading cause of cancer-related death in children and young adults, recent studies have identified profound alterations in iron homeostasis at both cellular and microenvironmental levels. These include increased iron uptake, disrupted storage and export, and a reliance on iron-dependent metabolic pathways that promote proliferation, metastasis, and immune evasion. Despite advances in surgical and chemotherapeutic approaches, survival out-comes in OS have stagnated, underscoring the need for novel therapeutic strategies. Tar-geting iron metabolism represents a promising avenue, with strategies such as iron chela-tion, transferrin receptor inhibition, ferroptosis induction, and modulation of ferritinoph-agy, showing preclinical efficacy. In this review, we explore the multifaceted role of iron in OS pathogenesis, dissect emerging therapeutic approaches aimed at disrupting iron reg-ulatory networks, and highlight innovative delivery platforms including nanomedicine. By integrating current knowledge on iron metabolism with the molecular complexity of OS, we present a comprehensive perspective that may help in the development of new treatments aimed at overcoming drug resistance, ultimately improving clinical outcomes for OS patients.