HMOX1 and familial pancreatic carcinoma: Ref-1/APE1 regulates both the transcriptional activity and DNA repair signaling activity of the tumor suppressor p53.16, 156, 157 Additionally, Ref-1/APE1’s redox function negatively regulates transcription factor nuclear factor erythroid-related factor 2 (NRF2).17 NRF2’s cytoprotective functions include regulation of oxidative stress; however, NRF2 also upregulates HMOX-1, a pro-tumorigenic gene responsible for treatment resistance.158 Combined inhibition of HMOX-1 and Ref-1/APE1’s redox activity has been shown to synergistically kill pancreatic cancer cells.17