Copper‐Related Cell Death and the Role of Copper in Head and Neck Squamous Cell Carcinoma and Therapeutic Strategies

Abstract As an essential mineral element for the human body, copper (Cu) is necessary for various physiological functions. Excess or deficiency of copper causes cytotoxicity and damages the body. Thus, strict regulatory mechanisms are required to maintain copper homeostasis. Copper correlates closely with many forms of cell death. A recent study found that copper‐dependent cell death, known as cuproptosis, is different from all other known forms of cell death. This discovery helps us further understand the role of copper in cytotoxicity. Copper dysregulation occurs in a variety of malignancies, including head and neck squamous cell carcinoma (HNSCC), which is the eighth most common malignancy worldwide. This may increase the risk of HNSCC from a population perspective. Further exploring molecular mechanisms of copper in HNSCC will contribute to provide new therapeutic opportunities. Here, the physiological metabolism and functions of copper, as well as copper‐related cell death, are reviewed. The study focuses on the research advances of copper in HNSCC, including the epidemiology and molecular mechanisms, as well as therapeutic strategies targeting copper homeostasis.