Given their multifaceted roles, integrative profiling of NRF2 and NOTCH alterations, at genomic, transcriptomic, and protein levels, could improve patient stratification and guide the development of combination strategies (e.g., NRF2 or NOTCH inhibitors with ICIs or standard therapies) aimed at overcoming resistance and improving durable clinical responses in lung cancer. Here, NFE2L2 is linked to lung cancer.