The earliest report on drug resistance was conducted by Tsutomu Ohta et al., who reported that KEAP1 mutations located within the IVR and DGR domains occurred in a subset of Japanese lung cancer patients (3/29, 10%), leading to the attenuated inhibition of KEAP1 and the enhanced transcriptional activity of NRF2, giving rise to growth advantages and cisplatin resistance in cancer cells [55]. This evidence concerns the gene NFE2L2 and lung cancer.