STAT3 and cancer: One of the most lethal cancers, pancreatic ductal adenocarcinoma (PDAC) has a 5-year mortality rate of ~92% and is characterized by a complex TME, heterogeneity within the tumor, extreme hypoxia, and an inherent ability to metastasize.180–183 The regulation of HIF-1α, STAT3, AP-1, and NF-κB by Ref-1/APE1 indicates that inhibition of Ref-1/APE1 redox signaling has potential clinical utility in PDAC.