These para-inflammatory states, which can originate in a NF-κB-independent cell-autonomous manner (e.g., SIR) or in a more systemic NF-κB-dependent manner (Soria-Valles et al., 2016), would operate as senescence-inflammatory friend-or-foe switches that, while originally contributing to tissue protective senescence and counteracting tumor progression, can also drive reprogramming-refractory aging phenotypes and cancer-prone epithelial tissue (Figure 2). This evidence concerns the gene NFKB1 and neoplasm.