"Pancreatic Adenocarcinoma".pdf

Pancreatic ductal adenocarcinoma is the most lethal common cancer due to late diagnosis and resistance to therapy. The median age at diagnosis is 71 years, and the incidence ranges from 1 to 10 cases per 100,000 people, with a higher rate in developed countries and among men. Risk factors include smoking, long-standing diabetes mellitus, nonhereditary and chronic pancreatitis, obesity, and family history. The disease is characterized by activating mutations in KRAS, progression from precursor lesions, local invasion, distant metastasis, and evasion of tumor immunity. Molecular pathology studies have established a model of progression from low-grade to high-grade pancreatic intraepithelial neoplasia, with accumulating genetic alterations. Recent exome-sequencing studies have identified additional loss-of-function mutations, and genetically engineered mouse models support this model of genetic progression. Intraductal papillary mucinous neoplasms are a second type of precursor to pancreatic cancer, with heterogeneous histologic and clinical features. Genomics analyses have focused on resected pancreatic adenocarcinoma, showing considerable intratumoral genomic heterogeneity and overlapping genomic features between primary tumors and metastatic deposits.