NF-κB signaling in prostate cancer: A promising therapeutic target?

Prostate carcinoma (PCa) displays a wide variety of genetic alterations, versatile expression profiles as well as cell surface markers. Despite this heterogeneity, a common treatment for advanced PCa is androgen deprivation therapy (ADT). ADT targets the androgen receptor-a member of the nuclear receptor superfamily-which is required for development and function of the prostate and critical for PCa growth and survival. After an initial regression of the tumor during ADT, a large fraction of tumors progress to so-called castration-resistant prostate carcinoma (CRPca) which is highly resistant toward chemotherapy. The ensuing high mortality rates illustrate the importance of novel therapeutic targets for CRPCa. The transcription factor NF-kappa B was recently proposed as such a potential target for therapeutic intervention in CRPCa. Although NF-kappa B is essential for the regulation of innate and adaptive immunity recent data suggest a role of NF-kappa B in cancer initiation and progression. However, the exact function of NF-kappa B signaling in PCa is still a matter of debate. Here, we review known roles of NF-kappa B signaling in PCa and emphasize the crosstalk of NF-kappa B and androgen receptor signaling. Finally, we discuss potential therapeutic relevance of blocking NF-kappa B in PCa.