Post-Translational Modifications in Pancreatic Cancer: Mechanisms to Clinical Applications.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, characterized by an extremely low 5-year survival rate. Its aggressiveness is attributed to early metastasis, rapid progression, and resistance to conventional therapies. Post-translational modifications (PTMs), which involve covalent modifications of amino acid residues, dynamically regulate protein activity, stability, and interactions. Increasing evidence has identified PTMs as key drivers in the pathogenesis of PDAC. PTMs encompass classical modifications such as phosphorylation, acetylation, glycosylation, ubiquitination, and methylation, as well as emerging modifications including SUMOylation, lysine crotonylation, and palmitoylation. This review first summarizes the mechanistic roles of both classical and novel PTMs in PDAC. It then explores the crosstalk among different types of PTMs and their integrated impact on PDAC progression. Finally, this review provides a theoretical basis for identifying early diagnostic biomarkers and potential targets for personalized therapy in PDAC. Overall, this work lays a conceptual foundation for future studies aimed at deciphering the complex PTM networks and their contributions to PDAC malignancy.