The Evolving Landscape of microRNAs in Cholangiocarcinoma and Pancreatic Cancer

Cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies with limited therapeutic options and poor prognoses. In recent years, microRNAs (miRNAs) have gained attention as key molecular regulators involved in tumor progression, chemoresistance, and metastasis. This review explores the diagnostic, prognostic, and therapeutic potential of miRNAs in CCA and PDAC, emphasizing their shared and distinct molecular pathways and their utility in the context of precision oncology. Several dysregulated miRNAs, most notably miR-21 and miR-155, are overexpressed in both cancers and contribute to activation of oncogenic pathways such as PI3K/AKT signaling, epithelial–mesenchymal transition, and inflammatory cascades. miR-21, in particular, is associated with resistance to gemcitabine and cisplatin. In contrast, tumor-suppressive miRNAs such as miR-34a and miR-145 are often downregulated, and their restoration using synthetic mimics has demonstrated promising antitumor effects in preclinical studies. Moreover, circulating miRNAs show potential as non-invasive biomarkers for early detection and disease monitoring. Advanced delivery platforms, including nanoparticles and exosome-based systems, are being developed to improve the stability and tumor specificity of miRNA-based therapeutics. miRNAs represent a promising class of molecules in the diagnosis, stratification, and treatment of CCA and PDAC. Their dual role as biomarkers and therapeutic agents positions them at the intersection of molecular pathology and personalized medicine. Further multicenter clinical trials and mechanistic studies are needed to validate their clinical applicability and to refine delivery strategies for targeted miRNA modulation.