Because of the pathways it affects, Ref-1/APE1 is seen as a critical node in tumor signaling (Fig. 2) and thus is a prime target for anticancer therapy.2, 3, 19, 21 However, teasing apart Ref-1/APE1’s activities to create a specific inhibitor that targets only its endonuclease or redox function is challenging. This evidence concerns the gene APEX1 and neoplasm.