Targeting the NF-κB pathway in prostate cancer: a promising therapeutic approach?

Author(s): Daniela Verzella, Mariafausta Fischietti, Daria Capece, Davide Vecchiotti, Filippo Del Vecchio, Germana Cicciarelli, Valentina Mastroiaco, Alessandra Tessitore, Edoardo Alesse and Francesca Zazzeroni

Volume 17, Issue 3, 2016

Page: [311 - 320] Pages: 10

DOI: 10.2174/1389450116666150907100715

Price: $65

Abstract

Rel/NF-κB transcription factors are key regulators of genes implicated in inflammatory and immune activation, cell growth and protection from apoptosis. Constitutive activation of NF-κB has been observed in several types of cancers. Recently, it has been shown that inflammation and cancer are molecularly linked by means of NF-κB. During prostate cancer progression, NF-κB promotes cell survival, tumor invasion, metastasis and chemoresistance. NF-κB constitutive activation has been frequently demonstrated in primary prostate cancers and it correlates with loss of androgen receptor expression and castration-resistant phenotypes. Indeed, inhibition of NF-κB pathway may reduce the oncogenic effects mediated by chronic inflammatory response. Therefore, NF-κB represents a hopeful target for the treatment of prostate cancer due to its role in oncogenesis and chemoresistance. Here, the current knowledge about the roles of NF-κB signaling pathway in prostate tumorigenesis is discussed, taking into consideration the potentiality and effectiveness of NF-κB inhibitors as therapeutic agents for prostate cancer.

Keywords: Prostate cancer, NF-κB, IKK, NF-κB inhibitors, proteasome inhibitors, IKK inhibitors, anti-inflammatory drugs.

Graphical Abstract

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