Unraveling the therapeutic landscape of miRNAs in pancreatic cancer.

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), remains one of the deadliest malignancies with a dismal prognosis due to late diagnosis and limited effective treatments. This review explores the multifaceted role of circulating and exosomal microRNAs (miRNAs) in pancreatic cancer progression, metastasis, diagnosis, prognosis, and therapeutic potential. miRNAs-a class of small non-coding RNAs-regulate gene expression post-transcriptionally, influencing key oncogenic and tumor-suppressor pathways. Dysregulated miRNA expression correlates with tumor stages, metastasis, and patient survival, presenting promising biomarkers for early detection and monitoring disease progression. Oncogenic miRNAs like miR-21 and miR-10b are elevated in the serum exosomes of PDAC patients and contribute to tumor growth and therapy resistance by modulating pathways such as Ras/ERK and promoting epithelial-mesenchymal transition. Advances in combining miRNA profiles with traditional markers have significantly improved diagnostic accuracy, highlighting miRNAs as robust tools for early intervention. Furthermore, targeting miRNAs therapeutically, either through anti-miRNA oligonucleotides or modulation of their regulatory networks, offers novel approaches to overcome chemoresistance and impede tumor progression. This review synthesizes current understanding and emerging insights into miRNA-driven molecular mechanisms in pancreatic cancer, underscoring their critical role in shaping future diagnostic and therapeutic landscapes.