Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

• Published in: Clinical and translational medicine Vol. 14; no. 6; pp. e1724 - n/a
• Main Authors: Wang, Yuhong, Pei, Pei, Yang, Kai, Guo, Lingchuan, Li, Yuan
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2024; John Wiley and Sons Inc; Wiley
• Subjects: Apoptosis; Biomarkers; cancer therapy; Cell death; Cell Proliferation - drug effects; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Copper; Copper - metabolism; cuproptosis; Cytochrome; Disease; Enzymes; Ferroptosis; Genes; Homeostasis; Humans; Lipids; Medical research; Metabolism; Metastasis; Mutation; Proteins; Review; Reviews; Sulfur; Toxicity; cancer therapy; copper; colorectal cancer; cuproptosis
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.1724

Copper, a trace element and vital cofactor, plays a crucial role in the maintenance of biological functions. Recent evidence has established significant correlations between copper levels, cancer development and metastasis. The strong redox‐active properties of copper offer both benefits and disadvantages to cancer cells. The intestinal tract, which is primarily responsible for copper uptake and regulation, may suffer from an imbalance in copper homeostasis. Colorectal cancer (CRC) is the most prevalent primary cancer of the intestinal tract and is an aggressive malignant disease with limited therapeutic options. Current research is primarily focused on the relationship between copper and CRC. Innovative concepts, such as cuproplasia and cuproptosis, are being explored to understand copper‐related cellular proliferation and death. Cuproplasia is the regulation of cell proliferation that is mediated by both enzymatic and nonenzymatic copper‐modulated activities. Whereas, cuproptosis refers to cell death induced by excess copper via promoting the abnormal oligomerisation of lipoylated proteins within the tricarboxylic acid cycle, as well as by diminishing the levels of iron‐sulphur cluster proteins. A comprehensive understanding of copper‐related cellular proliferation and death mechanisms offers new avenues for CRC treatment. In this review, we summarise the evolving molecular mechanisms, ranging from abnormal intracellular copper concentrations to the copper‐related proteins that are being discovered, and discuss the role of copper in the pathogenesis, progression and potential therapies for CRC. Understanding the relationship between copper and CRC will help provide a comprehensive theoretical foundation for innovative treatment strategies in CRC management. Physiological state copper ion transport process in vivo The role of copper ions in the carcinogenesis and development of colorectal cancer Copper ions mediate a variety of cell death modes The role of targeted copper ions in the diagnosis and treatment of colorectal cancer