biostudies-literatureUnknown86Kiran SPancreatic ductal adenocarcinoma (PDAC) remains highly resistant to therapy, surviving despite hypoxia, oxidative stress, and nutrient deprivation. Redox effector factor-1 (Ref-1) regulates several oncogenic transcription factors (TFs) and is controlled by peroxiredoxins (PRDX). We investigated how Ref-1 inhibition by APX2014, combined with PRDX expression, affects pancreatic cancer cells from multiple patient lines. Silencing or CRISPR/Cas9 knockout of PRDX1-but not PRDX2-6-sensitized PDAC cell lines to APX2014 both in vitro and in vivo without affecting Ref-1's DNA repair function of apurinic/apyrimidinic endonuclease. The combination of PRDX1 loss and APX2014 treatment increased apoptosis and decreased TF activity (NF-κB, HIF-1α) and their downstream targets, TNFAIP2, Survivin, and CA9.Redox biology103848https://www.ebi.ac.uk/biostudies/studies/S-EPMC12445586biostudies-literatureThe absence of Peroxiredoxin-1 in human pancreatic ductal adenocarcinoma (PDAC) markedly reduces cell survival and tumor growth when coupled with the inhibition of Ref-1 redox signaling.PMC12445586Kiran SKelley MRHaiaty SPeil JWireman RSFishel MLPotchanant ESCao SMitchell DKVilseck JZGeorgiadis MMRai RfalseThe absence of Peroxiredoxin-1 in human pancreatic ductal adenocarcinoma (PDAC) markedly reduces cell survival and tumor growth when coupled with the inhibition of Ref-1 redox signaling.Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to therapy, surviving despite hypoxia, oxidative stress, and nutrient deprivation. Redox effector factor-1 (Ref-1) regulates several oncogenic transcription factors (TFs) and is controlled by peroxiredoxins (PRDX). We investigated how Ref-1 inhibition by APX2014, combined with PRDX expression, affects pancreatic cancer cells from multiple patient lines. Silencing or CRISPR/Cas9 knockout of PRDX1-but not PRDX2-6-sensitized PDAC cell lines to APX2014 both in vitro and in vivo without affecting Ref-1's DNA repair function of apurinic/apyrimidinic endonuclease. The combination of PRDX1 loss and APX2014 treatment increased apoptosis and decreased TF activity (NF-κB, HIF-1α) and their downstream targets, TNFAIP2, Survivin, and CA9.2025-01-01T00:00:00Z2025 Sep2026-06-03T14:30:27.152Z2026-04-28T03:11:42.384ZS-EPMC124455864090231910.1016/j.redox.2025.103848