Undoubtedly, the targeting of upstream signalling mechanisms and protein-protein interactions governing the contextual and tissue-specific activation of NF-κB signalling and, at the opposite end of the spectrum, the non-redundant effectors of the diverse tissue-specific transcriptional programmes that NF-κB activates in order to exert its biological functions are amongst the most attractive strategies being developed to achieve contextual, cancer-cell selective therapeutic inhibition of the NF-κB pathway, and thereby circumvent the preclusive limitations of conventional NF-κB inhibitors. The gene discussed is NFKB1; the disease is cancer.