Pancreatic cancer: disease dynamics, tumor biology and the role of the microenvironment.

Pancreatic cancer is known for its propensity to metastasize. Recent studies have challenged the commonly held belief that pancreatic cancer is a stepwise process, where tumor cells disseminate late in primary tumor development. Instead it has been suggested that pancreatic tumor cells may disseminate early and develop independently and in parallel to the primary tumor. Circulating tumor cells can be found in most patients with pancreatic cancer, even in those with localized stage. Also, recent phylogenetic analyses have revealed evidence for a branched evolution where metastatic lineages can develop early in tumor development. In this Review, we discuss current models of pancreatic cancer progression and the importance of the tumor microenvironment, in order to better understand the recalcitrant nature of this disease.