Lee Dung-Fang, Hung Mien-Chie
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2008 Sep 15;14(18):5656-62. doi: 10.1158/1078-0432.CCR-08-0123.
IkappaB kinases (IKK) and IKK-related kinases play critical roles in regulating the immune response through nuclear factor-kappaB 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 IKK and IKK-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 IKK and IKK-related kinases, and outline the strategies used for targeting IKK as a therapeutic intervention for cancer.
IκB激酶(IKK)及IKK相关激酶通过核因子-κB和干扰素调节因子依赖性信号转导级联反应在调节免疫应答中发挥关键作用。最近,这些激酶与包括癌症在内的多种人类疾病的发病机制有关。事实上,IKK活性失调会促进肿瘤存活、增殖、迁移、转移及血管生成,这些都是多种人类癌症的共同特征。由于它们在人类癌症发展中的致癌作用,靶向IKK及IKK相关激酶正日益成为开发新型癌症治疗干预措施的热门途径。本综述将简要介绍IKK及IKK相关激酶下游底物的最新发现,并概述将靶向IKK作为癌症治疗干预措施所采用的策略。