61 Recent studies have highlighted the paradoxical nature of copper in cancer treatment. While essential for cellular processes, copper can both promote and inhibit tumour growth, depending on its concentration and the cellular context. The new ideas of “cuproplasia” and “cuproptosis” explain these two functions. “Cuproplasia” refers to cell growth that depends on copper, and “cuproptosis” describes a new way that mitochondrial cells die when they get too much copper. The findings were published in the journal Nature Reviews Clinical Oncology. Copper, a trace element, is vital for various biochemical processes, including mitochondrial respiration and antioxidant defence. But maintaining copper homeostasis is crucial, as both deficiency and excess can be detrimental. Dysregulated copper metabolism has been observed in many cancers, making it a target for potential therapeutic interventions. Cuproplasia refers to the role of copper in enhancing cellular proliferation. This process involves copper’s participation in enzymatic activities and signalling pathways that drive tumour growth. For example, high copper levels have been linked to higher levels of the copper transporter SLC31A1 in a number of cancers. This makes it easier for the cancer cells to take in copper, which helps them grow. Colorectal cancer cells with the KRASG12V mutation have also been shown to use macropinocytosis, an endocytic pathway, to take in more copper, which helps the tumour grow. Research has shown that high copper levels can exacerbate cancer. For example, chronic exposure to elevated copper concentrations accelerates tumour growth in preclinical models of pancreatic islet cell carcinoma and breast cancer. These findings underscore the importance of copper in tumour biology and raise concerns about the potential risks of copper overexposure. On the flip side, copper can also induce cell death, a process termed cuproptosis. Cuproptosis is different from apoptosis and necrosis because it is caused by copper building up in the mitochondria. This makes iron-sulfur cluster proteins less stable and lipoylated proteins stick together. This disruption of mitochondrial function ultimately results in proteotoxic stress and cell death. The discovery of cuproptosis opens new avenues for cancer therapy. Targeting this pathway could selectively induce death in cancer cells with high copper dependency. For instance, the copper ionophore elesclomol has been shown to enhance the cytotoxic effects of copper by facilitating its transport into mitochondria. This approach holds promise, particularly in tumours with specific genetic profiles that render them more susceptible to copper-induced stress. The dual nature of copper in cancer — as both a promoter of tumour growth and a trigger of cell death — presents unique challenges and opportunities for therapy. Copper chelators, which bind and remove excess copper, can potentially suppress cuproplasia. On the other hand, copper ionophores, which increase intracellular copper levels, could induce cuproptosis and selectively kill cancer cells. Also, the activity of genes related to copper metabolism, like SLC31A1 and FDX1, may help doctors figure out if a patient is copper dependent and make personalised treatment plans. For example, patients with tumours exhibiting high SLC31A1 expression may benefit from therapies targeting copper uptake pathways. As researchers continue to unravel the complexities of copper metabolism in cancer, the development of robust assays and biomarkers to monitor copper levels and their impact on tumour biology will be crucial. Additionally, understanding the mechanisms underlying resistance to copper-based therapies will be vital for improving treatment efficacy.