Objectives: Clinical observations have demonstrated that copper levels elevate in several cancer types, and copper deprivation is shown to inhibit tumour angiogenesis and growth in both animal models and preclinical trials. However, the content of copper in pancreatic duct adenocarcinoma (PDAC) and whether it is a potential therapy target is still unknown.Materials and Methods: The levels of copper in PDAC specimens were detected by ICP‐MS assays. Copper depletion in Panc‐1 or MiaPaCa‐2 cells was conducted via copper transporter 1 (SLC31A1) interference and copper chelator tetrathiomolybdate (TM) treatment. The effects of copper deprivation on cancer cells were evaluated by cell proliferation, migration, invasion, colony formation and cell apoptosis. The mechanism of copper deprivation‐caused cancer cell quiescence was resolved through mitochondrial dysfunction tests and autophagy studies. The tumour‐suppression experiments under the condition of copper block and/or autophagy inhibition were performed both in vitro and in xenografted mice.Results: SLC31A1‐dependent copper levels are correlated with the malignant degree of pancreatic cancer. Blocking copper absorption could inhibit pancreatic cancer progression but did not increase cell death. We found that copper deprivation increased mitochondrial ROS level and decreased ATP level, which rendered cancer cells in a dormant state. Strikingly, copper deprivation caused an increase in autophagy to resist death of pancreatic cancer cells. Simultaneous treatment with TM and autophagy inhibitor CQ increased cell death of cancer cells in vitro and retarded cancer growth in vivo.Conclusions: These findings reveal that copper deprivation‐caused cell dormancy and the increase in autophagy is a reason for the poor clinical outcome obtained from copper depletion therapies for cancers. Therefore, the combination of autophagy inhibition and copper depletion is potentially a novel strategy for the treatment of pancreatic cancer and other copper‐dependent malignant tumours.

Statins, known as HMG-CoA reductase (HMGCR) inhibitors, have primarily been utilized for metabolic and angiographic medical applications because of their cholesterol-lowering effects. Similar to other drugs, statins may also induce a series of potential side effects. Statins inhibit the HMGCR (rate-limiting enzyme) activity in early stages of mevalonate pathway and then indirectly affect a number of intermediate products, including non-sterol isoprenoids (coenzyme Q10, dolichol etc.), which can result in impaired functions of body organs. Recently, scores of studies have uncovered additional functional mechanisms of statins in other diseases, such as diabetes mellitus, nervous system diseases, coronary heart disease, inflammation and cancers. This review aims to summarize the positive and adverse mechanisms of statin therapy. Statin care should be taken in the treatment of many diseases including cancers. Since the underlying mechanisms are not fully elucidated, future studies should spend more time and efforts on basic research to explore the mechanisms of statins.

SLC7A11: also known as Sodium-Coupled Neutral Amino Acid Transporter 11, is an essential transporter protein that plays a vital role in the intracellular transport of amino acids, especially cysteine. Recently, its involvement in cell death mechanisms has attracted considerable interest, underscoring its significance in both normal physiological functions and various disease states. This paper aims to provide a thorough overview of current understanding of the role of SLC7A11 in two specific types of cell death: disulfidptosis and ferroptosis. We highlight the dual functions of SLC7A11 in these processes, examining how its activity changes under different pathological conditions and what this means for potential therapeutic approaches. In this study, we clarify the regulatory mechanisms governing SLC7A11 and its influence on cell death, ultimately presenting new insights that could guide future research in targeted therapies.