PPARδ: An underappreciated tumor accelerator in pancreatic ductal adenocarcinoma

Pancreatic cancer, primarily pancreatic ductal adenocarcinoma (PDAC), is one of the leading causes of cancer-related death, largely due to its late diagnosis and highly aggressive nature. Although precursors such as pancreatic intraepithelial neoplasia (PanIN), often harboring KRAS mutations, are commonly detected in adults; PanIN rarely progresses to invasive PDAC. The molecular mechanisms that govern this PanIN-to-PDAC transition remain poorly understood. Peroxisome proliferator-activated receptor delta (PPARδ), a ligand-activated nuclear transcription factor, plays critical roles in lipid metabolism, inflammation and tumorigenesis across multiple cancer types. In this brief review, we summarize recent advances and emerging evidence implicating PPARδ activation in oncogenic KRAS-initiated pancreatic tumorigenesis and progression, with emphasis on mechanisms such as metabolic reprogramming and immune suppression. These integrated insights underscore PPARδ as a potential therapeutic target in this lethal malignancy.