APEX1 and cancer: Colon cancer, the second leading cause of cancer related death in the U.S.,175 exhibits increased levels of cytoplasmic Ref-1/APE1.176 In liver tumor tissue of metastasized colorectal cancer, increased Ref-1/APE1 expression corresponds to poor patient outcome.177 In colony-forming assays, siRNA Ref-1/APE1 knockdown significantly increases the sensitivity of colon cancer cells to ionizing radiation (IR).