NFE2L2 and cancer: Four major mechanisms that regulate 6-PGDH hyperactivation in cancer have been reported: YTH domain family 2 promotes 6-PGDH mRNA translation by directly binding to the m6A modification site [20], nuclear factor erythroid 2-related factor 2 activates 6-PGDH via a well-conserved anti-oxidant response element [21], epidermal growth factor receptor phosphorylates and activates 6-PGDH by Fyn [18], and direct structural interactions with malic enzyme1 [22].