Aberrant Signal Transduction Pathways in Pancreatic Ductal Adenocarcinoma: Current Perspectives on Molecular Targets

Abstract

Pancreatic cancer is among the most aggressive neoplasms worldwide, with a significantly low five-year survival rate as reported in the literature. Pancreatic tumours are predominantly diagnosed as pancreatic ductal adenocarcinoma (PDAC), which is characterized by poor prognosis, late diagnosis, aggressive progression, and resistance to standard chemotherapy. Recent advances in the field of molecular and genomic biology have improved the understanding of the genetic underpinnings of this disease. The review discusses the key genetic drivers of pancreatic carcinogenesis, including KRAS, TP53, CDKN2A, SMAD4, and BRCA1/2. The mechanisms of action of these genes and their impact on the signaling pathways involved in the development and progression of PDAC are described. These genes encode proteins that participate in the regulation of the MAPK signaling pathway, cell cycle progression, TGF-β signaling pathway, and homologous recombination DNA repair mechanisms. The review emphasizes the role of these genes as therapeutic biomarkers for the development of targeted molecular therapy. The current management strategies targeting these mechanisms and the emerging therapeutic agents that may be considered in the future for the management of patients with pancreatic cancer are discussed.