NFE2L2 and cancer: Another enzyme, 6PGD, which catalyzes the oxidative decarboxylation of 6-phosphogluconate (6-PG) to produce a second NADPH, also plays a role in chemotherapy resistance in cancer and can be hyperactivated by many pathways, such as the KEAP1/NRF2/ARE pathway, m6A mRNA methylation, EGFR-mediated phosphorylation, and ME1-mediated allosteric activation [225].