Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer

Cuproptosis, a recently identified copper-dependent form of regulated cell death, is driven by mitochondrial dysfunction caused by copper overload. Cuproptosis results from proteotoxic stress, which is triggered by copper-induced aggregation of lipoylated tricarboxylic acid (TCA) cycle enzymes and destabilization of iron-sulfur cluster proteins. This review elucidates the mechanisms of cuproptosis, emphasizing its regulation by copper homeostasis, metabolic reprogramming, and key signaling pathways such as p53, HIF-1α, Wnt/β-catenin, and AKT. Notably, copper modulates antitumor immunity through its effects on the tumor microenvironment, suggesting a critical role in cancer immunotherapy. Therapeutic strategies…

• NN
  National Natural Science Foundation of China

  Awards: 82173022, 82403120, 82472714, 82273098