Here, the inhibition of NRF2, either by treatment with Brusatol or by restored expression of wild-type KEAP1, suppressed tumor cell proliferation and tumorigenicity in vitro and in vivo, confirming that deregulation of the NRF2/KEAP1 pathway can be responsible for the acquired resistance to EGFR-TKIs observed in many NSCLC patients, while its pharmacologic ablation might represent a valid option to overcome this phenomenon [329]. This evidence concerns the gene NFE2L2 and neoplasm.