Preclinical studies show that the Ref-1/APE1 inhibitor APX3330 inhibits growth of pancreatic cancer-associated endothelial and endothelial progenitor cells.185 Additional studies demonstrate that APX3330 can reduce tumor endothelial VEGF secretion, blocking a potentially critical angiogenic ligand-receptor interaction in the TME.185 Based on these data and the regulation of key transcription factors implicated in PDAC, PDAC is one of the indications for APX3330 in clinical trials. This evidence concerns the gene APEX1 and familial pancreatic carcinoma.