The role of NF-kappaB/IkappaB proteins in cancer: implications for novel treatment strategies.

The nuclear factor-kappaB (NF-kappaB) family of transcription factors are involved in multiple cellular processes, including cytokine gene expression, cellular adhesion, cell cycle activation, apoptosis and oncogenesis. Constitutive activation of NF-kappaB has been described in a number of solid tumors and this activation appears to affect cancer cell survival. Inhibition of NF-kappaB has been shown to enhance the sensitivity of some cancer cell lines to antineoplastic- or radiation-induced apoptosis. Furthermore, suppression of NF-kappaB results in attenuation of cancer cachexia in a mouse tumor model. Studies are underway to further delineate the role of NF-kappaB in cancer cell survival, growth and resistance to standard chemotherapy and radiation regimens. Moreover, the effects of novel therapeutic agents which specifically target NF-kappaB proteins are currently being assessed in experimental models of cancer cell growth both in vitro and in vivo. In this review, we discuss the possible involvement of NF-kappaB in the growth of various solid tumors and potential future treatment strategies based on NF-kappaB inhibition.