Cuproptosis in hepatocellular carcinoma: bridging copper homeostasis with therapeutic horizons

Copper plays a pivotal role in human biology, participating in the synthesis of various enzymes and antioxidant reactions, which are crucial for processes such as cell proliferation, development, and immune regulation. The disruption of copper homeostasis is closely linked to a multitude of pathological conditions, particularly in the onset and progression of cancer. Abnormal copper metabolism not only affects the proliferation of tumor cells but may also alter the survival status of tumors by inducing cell death mechanisms, such as cuproptosis. Despite the diversity of current clinical treatment options for hepatocellular carcinoma (HCC), patient prognoses remain less than favorable. As a novel form of cell death, cuproptosis has garnered significant attention in HCC research, with preliminary studies indicating that its role in HCC could potentially impact the survival of tumor cells. In this review, we summarize the role of copper homeostasis, especially cuproptosis, in the pathogenesis, progression and potential treatment of HCC. Targeted interventions in copper metabolism, in conjunction with other HCC treatment strategies, could achieve precision therapy for HCC, establishing a foundation for future clinical strategies and paving the way for new possibilities in clinical treatment.