The IKK/NF-κB 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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.