Work

Innovative cross-intervention: copper ions and metabolic pathways in cancer therapy

Year: 2026

Type: article

Abstract: Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated. This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis, a regulated form of cell death triggered by copper accumulation. The mechanisms underlying copper homeostasis are detailed, including dietary absorption, systemic distribution, and intracellular utilization. Key transporters, such as copper transporter 1 (CTR1) and ATPase copper transporting alpha/b (ATP7A/B), are highlighted. Cancer cells often exhibit elevated copper levels, supporting proliferation and metastasis through pro-tumorigenic pathways. Recent studies have shown that disrupting copper homeostasis can induce cuproptosis, which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis. Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors, enhancing therapeutic efficacy through synergistic effects with reactive oxygen species (ROS) generation and immunomodulation. However, the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators. Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance. This review provides a comprehensive overview of copper metabolism in cancer, emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.

Source: Cancer Biology and Medicine

DOI: 10.20892/j.issn.2095-3941.2025.0198

Authors: Lili Niu, Wei Su, Lixia Ju, Jun Xiang, Zhou Yang, Bing Yao