Using the comprehensive TCGA data available through the cBioportal database (www.cBioportal.org)22, we examined DNA amplifications, deletions, and mutations in NRF2, KEAP1, and CUL3. When considering the cumulative alteration frequencies of all three genes as an overall assessment of pathway activation, the top two cancers of 31 surveyed malignancies were lung squamous cell carcinoma (35.96%) and lung adenocarcinoma (23.48%), the two main types of NSCLC, which are shown in Supplementary Fig. S1 (Panel A). Here, CUL3 is linked to cancer.