Pancreatic cancer: Molecular characterization, clonal evolution and cancer stem cells

Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause ofcancer-related death and is the most lethal of common malignancies with a five-year survivalrate of >10%. PDAC arises from different types of non-invasive precursor lesions: intraductalpapillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia.The genetic landscape of PDAC is characterized by the presence of four frequently-mutatedgenes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC hasgreatly contributed to the understanding of the molecular and cellular mechanisms through whichdriver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-drivengenetically-engineered mouse models that phenotypically and genetically recapitulate humanpancreatic cancer have clarified the mechanisms through which various mutated genes act inneoplasia induction and progression and have led to identifying the possible cellular origin ofthese neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for thedevelopment of personalized medicine strategies. The studies of the purification and characterizationof pancreatic cancer stem cells have suggested that a minority cell population is responsible forinitiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contributeto the identification and clinical development of more efficacious drug treatments.