Molecular insights into immune evasion and therapeutic paradigms in pancreatic cancer.

Abstract

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal malignancies, which is characterized by a complex tumor microenvironment (TME) that fosters immune evasion and treatment resistance. Recent genomic advancements have unveiled diverse molecular subtypes of PDAC, providing insights into targeted therapies and precision medicine. This review synthesizes the current understanding of PDAC's molecular characterization and immunosuppressive TME, as well as emerging therapeutic strategies, including innovative approaches targeting key molecular pathways such as kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), and immune checkpoints. Despite advances, challenges remain in overcoming treatment resistance and inherent heterogeneity of pancreatic cancer subtypes. We highlight the need for multidisciplinary collaboration to enhance early diagnosis and develop individualized therapeutic protocols, paving the way for improving the outcomes of this aggressive cancer. This integrated perspective underscores the urgency of transforming the innovative research into pancreatic cancer management.