Molecular biology and the diagnosis and treatment of adenocarcinoma of the pancreas

The diagnosis of infiltrating adenocarcinoma of the pancreas is associated with an overall 5-year survival of <5%. However, recent advances in surgical treatment of pancreatic cancer combined with the use of adjuvant chemoradiation therapy, have improved the outlook substantially. Although conventional pathologic features, such as tumor size, and status of surgical margins and lymph nodes have prognostic importance in patients with pancreatic cancer, novel approaches seem to be necessary to enhance our ability to predict outcome and select optimal therapies. In the case of colonic carcinoma, which has served as a paradigm for our understanding of the molecular basis of neoplasia, somatic mutations in critical oncogenes and tumor suppressor genes accompany progression from adenoma to carcinoma. A similar pattern is emerging for pancreatic cancer in that (a) there appears to be progression from intraductal lesions to infiltrating carcinoma, and (b) the K-ras oncogene and several tumor suppressor genes, including p53, deleted in colon cancer, and multiple tumor suppressor-1, are common targets of mutation and/or deletion. Cytogenetic and molecular studies of allelic loss suggest that additional oncogenes and tumor suppressor genes involved in the pathogenesis of pancreatic cancer remain to be discovered. These findings enhance our understanding of the etiology of pancreatic adenocarcinoma and serve as the basis for early detection and potentially for improved treatment of this commonly fatal malignancy.