The Regulation of Trace Metal Elements in Cancer Ferroptosis

Abstract Ferroptosis, as novel type of regulated cell death that has garnered widespread attention over the past decade, has witnessed the continuous discovery of an increasing number of regulatory mechanisms. Trace metal elements play a multifaceted and crucial role in oncology. Interestingly, it has been increasingly evident that these elements, such as copper, are involved in the regulation of iron accumulation, lipid peroxidation and antiferroptotic systems, suggesting the existence of “nonferrous” mechanisms in ferroptosis. In this review, a comprehensive overview of the composition and mechanism of ferroptosis is provided. The interaction between copper metabolism (including cuproptosis) and ferroptosis in cancer, as well as the roles of other trace metal elements (such as zinc, manganese, cobalt, and molybdenum) in ferroptosis are specifically focused. Furthermore, the applications of nanomaterials based on these metals in cancer therapy are also reviewed and potential strategies for co‐targeting ferroptosis and cuproptosis are explored. Nevertheless, in light of the intricate and ambiguous nature of these interactions, ongoing research is essential to further elucidate the “nonferrous” mechanisms of ferroptosis, thereby facilitating the development of novel therapeutic targets and approaches for cancer treatment.