Unveiling sex differences in pancreatic ductal adenocarcinoma: Current evidence and future directions (Review)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related death worldwide in both men and women. While sex-specific differences are increasingly recognized as critical determinants of health and disease, particularly in oncology, they remain markedly underexplored in PDAC. Emerging evidence suggests that sex differences influence numerous aspects of PDAC, including treatment response and prognosis. This knowledge gap represents a notable barrier to the development of effective, personalized therapeutic strategies for both sexes. The present review provides a comprehensive overview of the current knowledge on sex-based differences in PDAC, encompassing epidemiology, risk factors, chemotherapy pharmacokinetics and toxicity, prognosis, therapeutic response, immune interactions, tumor microenvironment, tumor microbiota and molecular biomarkers.