The IKK/NF-kappaB activation pathway-a target for prevention and treatment of cancer.
The importance of the IkappaB kinase (IKK)/NF-kappaB signaling pathway in immunoregulatory functions is well accepted. However, the relevance of IKK and NF-kappaB in tumor maintenance, tumor promotion and possibly even in tumor initiation is becoming more evident. Activation of the IKK/NF-kappaB signaling pathway leads to the induction of target genes that can interfere with apoptosis, cell cycle regulation, cell invasion and metastatic growth as well as radio- and chemotherapy. By possibly bridging inflammation and cancer NF-kappaB might also contribute to tumorigenesis. Several natural compounds and synthetic drugs that are able to inhibit the IKK/NF-kappaB activation pathway have been shown to either prevent cancer or to inhibit cell growth in animal models. However, these compounds do not selectively inhibit any of the NF-kappaB activation pathways. Furthermore, general inhibition of NF-kappaB might lead to immunodeficiency. The investigation of the different NF-kappaB signaling pathways in different cell types and their role in certain diseases is therefore needed to evaluate the most successful therapeutic strategies.
Greten
Florian R
FR
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.
Karin
Michael
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006801:Humans; D051550:I-kappa B Kinase; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human