Ferroptosis defense mechanisms: The future and hope for treating osteosarcoma.

Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron‐dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano‐drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions. Significance Statement: This article highlights some key challenges in osteosarcoma (OS) treatment, such as chemotherapy resistance, postoperative recurrence, and poor bone regeneration quality, and points out the urgent need to find more effective treatment options. It discusses ferroptosis, a form of iron‐dependent programmed cell death, which differs from other cell death mechanisms, demonstrating its unique value and potential in OS treatment. The importance of the article lies in its explanation of how the three major defense systems of ferroptosis not only can utilize traditional Chinese medicine, antitumor drugs, and nano‐drug carriers to induce ferroptosis in OS cells, but can also be combined with immunotherapy, differentiation therapy, and other treatment methods to significantly enhance chemotherapy sensitivity and inhibit tumor growth. This approach offers more choices and possibilities for the clinical treatment of OS, with significant prospects for clinical application and scientific research. Furthermore, the significance of the article is also evident in its promotion of the integration of traditional and modern medical methods, advocating for a multi‐angle, multi‐strategy comprehensive treatment approach to address complex medical issues. This interdisciplinary treatment strategy not only aids in developing new therapeutic drugs and methods but also provides new directions and insights for future OS research and treatment. [ABSTRACT FROM AUTHOR]