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

World J Urol. 2012 Jun;30(3):303-10. doi: 10.1007/s00345-011-0792-y. Epub 2011 Nov 16.

Abstract

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-κB was recently proposed as such a potential target for therapeutic intervention in CRPCa. Although NF-κB is essential for the regulation of innate and adaptive immunity recent data suggest a role of NF-κB in cancer initiation and progression. However, the exact function of NF-κB signaling in PCa is still a matter of debate. Here, we review known roles of NF-κB signaling in PCa and emphasize the crosstalk of NF-κB and androgen receptor signaling. Finally, we discuss potential therapeutic relevance of blocking NF-κB in PCa.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgen Receptor Antagonists / pharmacology
  • Androgen Receptor Antagonists / therapeutic use
  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Male
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / physiology*
  • Orchiectomy
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / physiopathology*
  • Prostatic Neoplasms / surgery
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Treatment Failure

Substances

  • Androgen Receptor Antagonists
  • NF-kappa B
  • Receptors, Androgen