Hadi Sadeghi, Moein Kohkalani, Seyyed Amin Seyyed Rezaei, Saba Kargarmonhaser, Faezeh Mahd Gharebagh, Amin Nikdouz, Arezoo Hosseini
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers globally, with a five-year survival rate of less than 10 % due to its symptomless progression and late-stage diagnosis. The tumor microenvironment (TME), dense with immune and stromal cells, plays a key role in facilitating tumor growth and resistance to conventional therapies. Genetic changes-namely, in KRAS, TP53, CDKN2A, and SMAD4-drive abnormal signaling through the MAPK/ERK, PI3K/AKT, and NF-κB pathways, among others, that contribute to PDAC aggressiveness. microRNAs (miRNAs), tiny non-coding regulators of gene expression, have emerged as paramount modulators in PDAC, functioning either as oncogenes or tumor suppressors. Their dysregulation not only affects hallmark cancer traits but also holds great promise for diagnosis and treatment. Therapy using miRNA mimics and inhibitors aims to restore gene expression balance, but delivery and stability concerns persist. Advances in nanotechnology are enabling increasingly targeted and effective miRNA-based therapies, potentially transforming the clinical management of pancreatic cancer (PC).