‘Divide and Conquer: Targeting the cell cycle in pancreatic cancer’

Pancreatic cancer has a very poor prognosis and new approaches to treatments are urgently needed as by current trends it will be the 2nd leading cause of cancer deaths in the United States. Recognizing that deregulated cell division is the hallmark of cancer we have interrogated different strategies to target the cell cycle for the treatment of pancreatic cancer. Firstly, KRAS oncogenic signaling induces replication stress in concert with deregulated proliferation. In principle this feature of pancreatic cancer can be targeted through the use of CHK inhibitors. Secondly, KRAS and additional genetic events that occur in pancreatic cancer coalesce in driving proliferation through deregulation of CDK4/6 activity. Thus, CDK4/6 inhibitors should be particularly effective in the treatment of pancreatic cancer. In spite of these rationales pancreatic cancer is particularly therapy recalcitrant and only through the use of unexpected combination approaches can strong therapeutic responses be observed.