Copper homeostasis and cuproptosis in gynecological cancers

Copper (Cu) is an essential trace element involved in a variety of biological processes, such as antioxidant defense, mitochondrial respiration, and bio-compound synthesis. In recent years, a novel theory called cuproptosis has emerged to explain how Cu induces programmed cell death. Cu targets lipoylated enzymes in the tricarboxylic acid cycle and subsequently triggers the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, leading to the loss of Fe-S clusters and induction of heat shock protein 70. Gynecological malignancies including cervical cancer, ovarian cancer and uterine corpus endometrial carcinoma significantly impact women's quality of life and even pose a threat to their lives. Excessive Cu can promote cancer progression by enhancing tumor growth, proliferation, angiogenesis and metastasis through multiple signaling pathways. However, there are few studies investigating gynecological cancers in relation to cuproptosis. Therefore, this review discusses Cu homeostasis and cuproptosis while exploring the potential use of cuproptosis for prognosis prediction as well as its implications in the progression and treatment of gynecological cancers. Additionally, we explore the application of Cu ionophore therapy in treating gynecological malignancies.