Metal-related cell death and its application in pancreatic cancer

As a highly aggressive tumour of the digestive tract, pancreatic cancer has a high mortality rate and poor treatment outcomes. The five-year survival rate for patients with pancreatic cancer is distressingly low, and the recurrence chance remains unacceptably high even with successful treatment. Surgical procedures and chemotherapy are the main treatments of pancreatic cancer, and surgical procedures are the only effective treatment at present. However, these cancer cells can easily develop resistance to chemotherapy agents, which leads to low treatment efficacy and high mortality in pancreatic cancer. Additionally, early diagnosis of pancreatic cancer is challenging due to the absence of obvious symptoms, making surgical intervention unattainable in early stages. However, pancreatic cancer cells show unique changes at genetic and cellular levels, which makes them sensitive to metalrelated cell death or exhibit some characteristics related to metalrelated cell death. These changes and characteristics could be utilized for treatment and diagnosis in pancreatic cancer.

Therefore, our motivation is to explain the potential of metalrelated cell death in treating this aggressive cancer. This review begins by analysing the types of metal-related cell death: ferroptosis, cuproptosis and lysozincrosis. Each form is evaluated based on its unique features and related metabolic pathways.

By examining the key characteristics of metal-related cell death modalities, their primary metabolic patterns and their interactions with pancreatic cancer, our aim is to point the direction to identify potential therapies and treatments.

Our review expands the possibilities for utilizing metal-related cell death and instils hope for its future potential in pancreatic cancer treatment.