Sex-Related Differences in Pancreatic Ductal Adenocarcinoma Progression and Response to Therapy

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with an increasing incidence rate and limited therapeutic options. Biological sex has an impact on many aspects of PDAC development and response to therapy, yet it is highly unappreciated in both basic and translational research, and worryingly in PDAC clinical trials. In this review, we summarize how biological sex influences PDAC incidence and mortality, genetic and epigenetic landscapes, anti-tumor immunity, responses to hormones, cachexia, and the efficacy of therapy. We highlight the importance of sex as a variable and discuss how to implement it into preclinical and clinical research. These considerations should be of use to researchers aiming at improving understanding of PDAC biology and developing precision medicine therapeutic strategies.