Pancreatic cancer genomics

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with the worst prognosis among all solid tumors [1]. Although surgical resection offers the only hope for cure, it is possible in only 20% of patients that present with local disease [2]. Indeed, most patients are diagnosed at an advanced stage, when the disease is inoperable. Whether dismal prognosis is a result of late diagnosis or early dissemination to distant organ is still a debate. Systemic chemotherapy provides temporary benefits in controlling advanced disease and prolonging survival in the adjuvant setting but this happens in a small proportion of patients. Several factors are supposed to contribute variably to the intrinsic chemotherapic resistance of pancreatic cancer and include: (i) the presence of a dense stromal component (termed desmoplastic reaction) that significantly reduces drug delivery [3]; (ii) the transformation of epithelial cells into a mesenchymal phenotype (referred to as epithelial to mesenchymal transition, EMT) [4]; and (iii) the presence of pancreatic cancer stem cells [5]. To complicate our understanding of chemoresistance, there is the marked molecular heterogeneity among primary tumors and metastatic deposits (discussed in details below) [6]. © 2013 Springer Science+Business Media Dordrecht. All rights are reserved.