Molecular Pathogenesis and Targeted Therapy of Pancreatic Cancer.

Accumulation of multiple genetic and/or epigenetic abnormalities is required for generation and progression of cancers, and the survival of cancer cells might depend on addiction to these abnormalities. Because disruption of such dependency on the abnormal molecules should cause the cancer cell death, so-called oncogene addiction is the rationale for molecular targeted therapy. Pancreatic cancer, especially pancreatic ductal adenocarcinoma, is one of the most lethal malignancies in humans, and remains a challenging problem in targeted therapy compared to other malignancies such as pancreatic neuroendocrine tumor. This review summarizes the molecular pathogenesis of pancreatic cancer on the basis of the recent studies of driver mutations including chromatin remodeling factors, and promising concepts "cancer stemness" and "stromal niche" for the strategy of novel targeted therapy.