Cell cycle machinery and its alterations in pancreatic cancer

Cancer is a disease of uncontrolled cell proliferation. Sequencing of the pancreatic cancer genome revealed frequent gene alterations that lead to constitutive proliferation signals and loss of the breaking systems. Cancer cells also display defects in the DNA repair systems, which suggest that compromised genome integrity contributes to the tumorigenesis process. These observations explain many of the abnormal behaviors of cancer cells, yet stopping proliferation of cancer cells remains a difficult task. This chapter will describe misregulation of the cell-cycle machinery in pancreatic cancer and therapeutic options to stop abnormal proliferation. The basic concept of the normal cell cycle will be outlined first, and the mechanisms of DNA repair will be introduced. Next, alterations of the cell cycle and DNA repair systems in pancreatic cancer will be described. Finally, therapeutic opportunities to target the specific alterations in the cell cycle and DNA repair systems in pancreatic cancer will be discussed.