Primers on Molecular Pathways -Cycling toward Pancreatic Cancer

Human cells divide and proliferate during the early stages of life to support development, and throughout adult life to support normal cellular turnover. Each dividing cell follows an orderly and tightly regulated series of events known as the cell cycle. This process ensures proper cellular division that maintains DNA and chromosomal integrity and responds appropriately to external signals which communicate the level of demand for new cells. In cancer, genetic mutations leading to the overexpression of proteins which support cell cycle progression, or the down regulation of proteins involved in cell cycle inhibition contributes to the dysregulated cellular division and proliferation of malignant cells. The resulting uninhibited cellular proliferation provides ample opportunity for additional genetic mutations that lead to tumor progression. In the following review, we provide a brief introduction to the cell cycle and a discussion of the mechanism underlying the dysregulation of the cell cycle in human cancer. We pay particular attention to pancreatic adenocarcinoma, an aggressive tumor that has a 5-year survival rate of 3-5%, and is the fourth leading cause of cancer mortality in the US.