APEX1 and cancer: Within the TME, there are several cell types that contribute to the growth and spread of pancreatic cancer: endothelial cells, pericytes, tumor-associated macrophages, lymphocytes, activated pancreatic stellate cells, and other cancer-associated fibroblasts (CAFs).182 The role of Ref-1/APE1 in the TME is still under investigation, but there is published evidence184 that Ref-1/APE1 can block endothelial cell function and suppress tumor-associated macrophages.