This indicates that NF-κB signaling is yet another cancer-associated pathway that relies on Ref-1/APE1.15, 18 Moreover, crosstalk between the STAT3 and NF-κB signaling pathways is well established, involving both feed-forward transcription of activating factors and STAT3/NF-κB complexes mediating co-transcription of tumor-promoting genes.47, 92–96 This provides further support for Ref-1/APE1 being a master regulator of both enzymes, a pivotal signaling node, and a worthy therapeutic target. This evidence concerns the gene STAT3 and neoplasm.