Harnessing downstream NF-κB signalling to achieve apoptosis-inducing anti-cancer-specific activity

Transcription factors of the NF-κB family are driven by many inflammatory stimuli and activate expression and production of soluble cytokines, chemokines and inflammatory mediators, and a plethora of important immune response genes.1 It has been known since long time that NF-κB is frequently activated in solid and blood cancer,2–3 stemming the idea that its oncogenic function relays on inhibition of cancerous cell death, driven either by antitumor drugs or tumour-suppressor mechanism.3 This hypothesis, robustly based on experimental models, originated the valid assumption that inhibiting NF-κB activity should be an effective therapeutic tool alone or in combination with chemotherapy or radiation therapy. This hypothesis ignited an intense race to develop NF-κB inhibitors, most often by targeting I-κB kinase, a protein kinase that is essential for NF-κB activation.