The transcription factors p53 and NFκB determine cellular fate and are involved in the pathogenesis of most-if not all-cancers. The crosstalk between these transcription factors becomes increasingly appreciated as an important mechanism operative during all stages of tumorigenesis, metastasis, and immunological surveillance. In this review, we summarize molecular mechanisms regulating cross-signaling between p53 and NFκB proteins and how dysregulated interactions between p53 and NFκB family members contribute to oncogenesis. We furthermore analyze how such signaling modules represent targets for the design of novel intervention strategies using established compounds and powerful combination therapies.
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