Biological and Clinical Impacts of Glucose Metabolism in Pancreatic Ductal Adenocarcinoma

Simple Summary Pancreatic ductal adenocarcinoma is a lethal cancer with high metastatic properties. While surgical treatment is considered the first choice, the difficulty associated with early diagnosis reduces the success rates of these interventions. Therefore, early diagnosis, and thus treatment, of pancreatic ductal adenocarcinoma is extremely important. Past studies have shown that most patients with pancreatic ductal adenocarcinoma have impaired glucose tolerance, while hyperglycemia also reportedly promotes various malignant behaviors in pancreatic cancer cells. This review summarizes the clinical and molecular impacts of glycolysis on pancreatic ductal adenocarcinoma, with the aim of providing an invaluable reference for, and novel insights regarding, pancreatic ductal adenocarcinoma research and treatment. Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type as it is prone to metastases and is difficult to diagnose at an early stage. Despite advances in molecular detection, its clinical prognosis remains poor and it is expected to become the second leading cause of cancer-related deaths. Approximately 85% of patients develop glucose metabolism disorders, most commonly diabetes mellitus, within three years prior to their pancreatic cancer diagnosis. Diabetes, or glucose metabolism disorders related to PDAC, are typically associated with insulin resistance, and beta cell damage, among other factors. From the perspective of molecular regulatory mechanisms, glucose metabolism disorders are closely related to PDAC initiation and development and to late invasion and metastasis. In particular, abnormal glucose metabolism impacts the nutritional status and prognosis of patients with PDAC. Meanwhile, preliminary research has shown that metformin and statins are effective for the prevention or treatment of malignancies; however, no such effect has been shown in clinical trials. Hence, the causes underlying these conflicting results require further exploration. This review focuses on the clinical significance of glucose metabolism disorders in PDAC and the mechanisms behind this relationship, while also summarizing therapeutic approaches that target glycolysis.

Automated summary

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type with high metastatic properties and difficulty in early diagnosis. Most PDAC patients have glucose metabolism disorders, which are closely related to the initiation, development, invasion, and metastasis of PDAC. This review provides valuable insights into the clinical and molecular impacts of glycolysis on PDAC research and treatment.