Molecular Biology of Pancreatic Cancer - New Aspects and Targets

Pancreatic ductal adenocarcinoma is a dismal disease with a median survival of less than 6 months and an overall 5-year survival rate less than 1% . This bad prognosis is due to early lymphatic and hematogenic dissemination. Effective therapies for locally advanced or metastatic tumors are very limited and curatively resected patients experience relapse in over 80% of cases. Together, these findings reflect the aggressive biology of the disease. Here, we describe molecular mechanisms leading to unrestrained proliferation, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, tissue invasion, metastasis and sustained angiogenesis. Potential therapeutic targets are highlighted. Pancreatic ductal adenocarcinoma (PDAC) is a chronic disease resulting from defective genome surveillance and signal transduction mechanisms. Key cellular processes, which were summarized by Hannahan and Weinberg as self- sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, tissue invasion and metastasis and sustained angiogenesis contribute to the emergence of this neoplasia and its malignant progression (1). This review will cover important new aspects of the molecular biology of the disease. For a comprehensive overview of the molecular biology of pancreatic ductal adenocarcinoma, we refer the reader to recent excellent reviews (2-4).