In large-cell neuroendocrine carcinomas (LCNECs), mutations in genes regulating NRF2 activity and members of the NOTCH receptor family are frequently observed, particularly in NSCLC-like LCNECs, where NOTCH pathway mutations help to discriminate them from classical adenocarcinomas [203]. This evidence concerns the gene NFE2L2 and non-small cell lung carcinoma.