For instance, NRF2 levels in pulmonary epithelial and colorectal cancer cells and the rat retina remain unchanged or are reduced during hypoxia43–45, suggesting that other transcription factors activated by hypoxia, such as nuclear factor kappa B (NF-κB) and forkhead box O3 (FoxO), primarily lead to increased antioxidant protein expression levels10. This evidence concerns the gene NFE2L2 and colorectal cancer.