Although NF-κB inhibition attenuates precancerous phenotypes (e.g., bortezomib reduces prostatic intraepithelial neoplasia formation in Foxp3-mutant mice),299 complete pathway ablation via the deletion of NF-κB essential modulator paradoxically accelerates pancreatic cancer progression and reduces the median lifespan despite reducing the early PanIN burden in young mice.300 This duality underscores the need for context-stratified targeting strategies that preserve tumor-suppressive senescence while inhibiting procarcinogenic inflammation. This evidence concerns the gene NFKB1 and familial pancreatic carcinoma.