Tamoxifen calms down the distressed PDAC stroma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human cancers and is associated with extensive desmoplastic changes in the tumor microenvironment. In this issue of EMBO Reports, two studies by Cortes et al 1, 2 identify the G‐protein‐coupled estrogen receptor (GPER) as an important regulator of the PDAC‐associated stroma, modulating tissue stiffness, hypoxic responses, and desmoplasia. Intriguingly, the authors find that tamoxifen, which is widely used for its antagonizing effect on nuclear estrogen receptor (ER)‐positive breast cancers, acts as GPER agonist to normalize the PDAC microenvironment. The two studies thus open up new opportunities to explore tamoxifen as potential anti‐stromal therapy in PDAC.