Recent insights into NF-κB signalling pathways and the link between inflammation and prostate cancer.
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.
Laboratory of Urological Oncology, Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY, USA; Department of Urology, University of Berne, Inselspital, Berne, Switzerland.
Daniel P
DP
Nguyen
Jinyi
J
Li
Shalini S
SS
Yadav
Ashutosh K
AK
Tewari
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology*
D000970:Antineoplastic Agents; D016328:NF-kappa B; D061988:Proteasome Inhibitors
IKK-α; NF-κB; apoptosis; castration-resistant; inflammation; metastasis; prostate cancer