Leveraging glycosylation for early detection and therapeutic target discovery in pancreatic cancer.

Abstract

Pancreatic cancer (PC) remains one of the most lethal malignancies, primarily due to late-stage diagnosis, limited biomarker specificity, and aggressive metastatic potential. Recent glycoproteomic studies have illuminated the crucial role of glycosylation in PC progression, revealing altered glycosylation patterns that impact cell adhesion, immune evasion, and tumor invasiveness. Biomarkers such as CA19-9 remain the clinical standard, yet limitations in sensitivity and specificity, especially in early disease stages, necessitate the exploration of alternative markers. Emerging glycoproteins-such as mesothelin, thrombospondin-2, and glycan modifications like sialyl-Lewis x-offer diagnostic promise when combined with CA19-9 or used in profiling panels. Furthermore, therapeutic strategies targeting glycosylation processes, including sialylation, and fucosylation, have shown potential in curbing PC metastasis and enhancing immune response. Translational platforms, such as patient-derived xenografts and advanced in vitro models, are pivotal in validating these findings and assessing glycosylation potential therapeutic impact. Continued exploration of glycosylation-driven mechanisms and biomarker discovery in PC can significantly advance early detection and treatment efficacy, offering new hope in the management of this challenging disease.