Understanding the stroma of pancreatic cancer: co-evolution of the microenvironment with epithelial carcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously therapy-resistant desmoplastic tumour. Antifibrotic therapy is shown to increase drug delivery in the preclinical setting. However, this approach can be a double-edged sword: first, PDAC is not uniform and some types of (dormant) stroma may in fact be protective; second, conventional chemotherapeutics are not powerful enough to eradicate all cancer cells in the tumour, therefore breaking down the stromal wall non-selectively may also lead to the increased dissemination of cancer cells. Recently, Kadaba et al have analysed the impact of the stromal cells in pancreatic, oesophageal and skin cancers, in bio-engineered, physiomimetic organotypic cultures. These authors show that the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when pancreatic stellate cells constitute the majority of the cellular population in a three-dimensional (3D) model. This work may be instrumental for better understanding the types of stoma in PDAC before eliminating it non-selectively.