If we collectively consider the mutations of the Cul3-KEAP1-Nrf2 axis, 64% and 34% of HNSCC and lung SCC patients have alteration of this pathway, respectively, and survival for patients harboring disruption to any component (KEAP1, Cul3 and/or RBX1) show poorer median survival compared with patients without alterations [71,79,80,81]. The gene discussed is CUL3; the disease is head and neck squamous cell carcinoma.