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.
Schwartz
S A
SA
Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Hernandez
A
A
Mark Evers
B
B
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D003043:Cocarcinogenesis; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007249:Inflammation / Q000235:genetics; D008967:Molecular Biology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D046988:Proteasome Endopeptidase Complex; D013256:Steroids; D014158:Transcription, Genetic / Q000235:genetics
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D020672:I-kappa B Proteins; D009097:Multienzyme Complexes; D016328:NF-kappa B; D013256:Steroids; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex