CUL3 and cancer: Paradoxically, however, in certain types of cancer the irreversible genetic upregulation of NRF2 resulting from stochastic somatic activating mutations in NFE2L2 or inactivating mutations in the gene encoding the repressor of NRF2, Kelch-like ECH-associated protein 1 (KEAP1), or that for its E3 ligase Cullin 3 (CUL3), is associated with progression of disease once it has been initiated [2].