Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11216
Revised: February 18, 2014
Accepted: April 15, 2014
Published online: August 28, 2014
Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.
Core tip: This review summarises current knowledge about the role of pancreatic stellate cells in production of cancer stroma, the mechanisms mediating stromal-tumour interactions and novel therapeutic approaches developed on the basis of our increasing understanding of the critical influence of stromal elements on disease progression.