Advances in targeting IKK and IKK-related kinases for cancer therapy

Abstract

IκB kinases (IKK) and IKK-related kinases play critical roles in regulating the immune response through nuclear factor-KB and IFN regulatory factor-dependent signaling transduction cascades. Recently, these kinases have been implicated in the pathogenesis of many human diseases, including cancer. In fact, dysregulation of IKK activities promotes tumor survival, proliferation, migration, metastasis, and angiogenesis-common characteristics of many types of human cancers. Because of their oncogenic effects in human cancer development, targeting lKK and lKK-related kinases is becoming an increasingly popular avenue for the development of novel therapeutic interventions for cancer. This review will briefly cover the recent discovery of the downstream substrates of lKK and IKK-related kinases, and outline the strategies used for targeting IKK as a therapeutic intervention for cancer. © 2008 American Association for Cancer Research.