Recent insights into NF‐κB signalling pathways and the link between inflammation and prostate cancer

• Published in: BJU international 2014-08, Vol.114 (2), p.168-176
• Main Authors: Nguyen, Daniel P., Li, Jinyi, Yadav, Shalini S., Tewari, Ashutosh K.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; apoptosis; Apoptosis - physiology; Biological and medical sciences; castration‐resistant; Gynecology. Andrology. Obstetrics; Humans; IKK‐α; inflammation; Inflammation - etiology; Inflammation - pathology; Male; Male genital diseases; Medical sciences; metastasis; Molecular Targeted Therapy; Nephrology. Urinary tract diseases; NF-kappa B - antagonists & inhibitors; NF-kappa B - physiology; NF‐κB; prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - etiology; Prostatic Neoplasms - pathology; Proteasome Inhibitors - therapeutic use; Signal Transduction - physiology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/bju.12488

Inflammation is involved in regulation of cellular events in prostate carcinogenesis through control of the tumour micro‐environment. A variety of bone marrow‐derived cells, including CD4+ lymphocytes, macrophages and myeloid‐derived suppressor cells, are integral components of the tumour micro‐environment. On activation by inflammatory cytokines, NF‐κB complexes are capable of promoting tumour cell survival through anti‐apoptotic signalling in prostate cancer (PCa). Positive feedback loops are able to maintain NF‐κB activation. NF‐κB activation is also associated with the metastatic phenotype and PCa progression to castration‐resistant prostate cancer (CRPC). A novel role for inhibitor of NF‐κB kinase (IKK)‐α in NF‐κB‐independent PCa progression to metastasis and CRPC has recently been uncovered, providing a new mechanistic link between inflammation and PCa. Expansion of PCa progenitors by IKK‐α may be involved in this process. In this review, we offer the latest evidence regarding the role of the NF‐κB pathway in PCa and discuss therapeutic attempts to target the NF‐κB pathways. We point out the need to further dissect inflammatory pathways in PCa in order to develop appropriate preventive measures and design novel therapeutic strategies.