APEX1 and neoplasm: Ref-1/APE1 overexpression has been postulated to play a role in the increased ability of tumor cells to grow and metastasize as a result of increased gene expression of genes that are directed by numerous critical transcription factors regulated by Ref-1/APE1.20 As discussed in Section II, numerous cancers have altered levels of Ref-1/APE1 expression (also see Table 2, Fig. 4).