Cuproptosis, a recently discovered form of cell death mediated by copper (Cu), has gained significant attention in cancer research due to its potential as an anti-cancer therapeutic. This article reviews the current understanding of cuproptosis, its mechanisms, and its applications in cancer treatment. Cuproptosis is characterized by the oligomerization of lipoylated proteins and the loss of iron-sulfur (Fe-S) protein clusters, leading to proteotoxic stress and cell death. The accumulation of Cu in tumor tissues has been observed in various cancers, suggesting a role in cancer progression. Cu can activate multiple signaling pathways, including receptor tyrosine kinase (RTK) signaling, phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling, and the BRAF signaling pathway, promoting cell proliferation, angiogenesis, and metastasis. However, excessive Cu can also induce tumor cell death through cuproptosis. Cu ionophores, such as disulfiram (DSF) and elesclomol (ES), have been identified as effective inducers of cuproptosis, with DSF and ES showing promise in cancer therapy. These compounds increase intracellular Cu levels, leading to the aggregation of lipoylated proteins and the loss of Fe-S cluster proteins, ultimately causing cell death. Nanotechnology-based approaches, such as Cu-doped nanomaterials, have also shown potential in delivering Cu to cancer cells and enhancing cuproptosis. Despite the promising results, challenges remain, including the need for better understanding of the optimal Cu concentration and the development of more effective drug delivery systems. Overall, the discovery and exploration of cuproptosis offer new avenues for cancer treatment, and further research is needed to optimize its therapeutic potential.Cuproptosis, a recently discovered form of cell death mediated by copper (Cu), has gained significant attention in cancer research due to its potential as an anti-cancer therapeutic. This article reviews the current understanding of cuproptosis, its mechanisms, and its applications in cancer treatment. Cuproptosis is characterized by the oligomerization of lipoylated proteins and the loss of iron-sulfur (Fe-S) protein clusters, leading to proteotoxic stress and cell death. The accumulation of Cu in tumor tissues has been observed in various cancers, suggesting a role in cancer progression. Cu can activate multiple signaling pathways, including receptor tyrosine kinase (RTK) signaling, phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling, and the BRAF signaling pathway, promoting cell proliferation, angiogenesis, and metastasis. However, excessive Cu can also induce tumor cell death through cuproptosis. Cu ionophores, such as disulfiram (DSF) and elesclomol (ES), have been identified as effective inducers of cuproptosis, with DSF and ES showing promise in cancer therapy. These compounds increase intracellular Cu levels, leading to the aggregation of lipoylated proteins and the loss of Fe-S cluster proteins, ultimately causing cell death. Nanotechnology-based approaches, such as Cu-doped nanomaterials, have also shown potential in delivering Cu to cancer cells and enhancing cuproptosis. Despite the promising results, challenges remain, including the need for better understanding of the optimal Cu concentration and the development of more effective drug delivery systems. Overall, the discovery and exploration of cuproptosis offer new avenues for cancer treatment, and further research is needed to optimize its therapeutic potential.