We provide proof-of-concept data that KRAS-mutant cancer cells can be targeted by combined inhibition of KRAS and HSP90/IKKα/IKKβ signaling, a strategy that blocks IL-1β-inducible oncogenic NF-κB activation and in vivo MPE development, a cancer phenotype that requires mutant KRAS-potentiated, IL-1β-induced IKKα activity. The gene discussed is NFKB1; the disease is cancer.