Research progress on the etiology and pathogenesis of pancreatic cancer: a narrative review

Pancreatic cancer (PC) is a highly malignant tumor of the digestive system, characterized by the lack of effective methods for early screening, diagnosis and treatment. Despite its low incidence rate, it has an extremely high mortality rate. In recent years, the number of confirmed cases worldwide has been on a continuous rise, making PC the sixth leading cause of cancer-related deaths across the globe. At present, clinical treatment strategies including surgical resection, chemotherapy, radiotherapy, molecular targeted therapy and biological immunotherapy have not significantly improved the survival prognosis of PC patients. Therefore, exploring safe and effective therapeutic approaches and clarifying the etiological mechanisms of PC have become key priorities in clinical treatment. Its occurrence and progression involve multilayered mechanisms, including environmental exposure, genetic susceptibility, metabolic abnormalities, chronic inflammation, progression of precancerous lesions, remodeling of the tumor microenvironment, and immune escape. Based on a summary of smoking, alcohol consumption, obesity, diabetes, chronic pancreatitis, genetic mutations, and multiple signaling pathways, this article further provides a critical review from the perspectives of evidence strength, mechanistic plausibility, and clinical translational value. It aims to deepen the understanding of the initiation and progression of pancreatic cancer and to provide new directions for its early diagnosis and precision treatment.