Overall, our study points to novel signaling cues in the interplay between STAT3/NF-κB pathways, estrogen signaling, and the lung tumor immune microenvironment in the pathogenesis of K-ras mutant lung cancer, thus offering opportune targets and/or strategies for new personalized therapies against this malignancy using already available agents (e.g. anti-IL-6 antibodies, STAT3 inhibitors, or HRT). This evidence concerns the gene NFKB1 and lung cancer.