Therapeutic implications of the nuclear factor-kappaB/nuclear receptor cross-talk.
More and more evidence reveals that the transcription factor NF-kappaB plays a critical role in tumor development and progression and that it may constitute the missing link between inflammation and cancer. It turned out that many of the well known cancer drugs exert their anti-tumoral effect at least in part through modulating the activity of NF-kappaB. The potential of nuclear receptors to modulate the activity of this widespread transcription factor has repeatedly been reported and illustrates their enormous therapeutic potential. However, the efficacy of these liganded receptors is overshadowed by the occurrence of unwanted effects owing to their broad range of actions. Accordingly, researchers pursue the ambition to improve the specificity of nuclear receptor modulators. In this review we have explored the molecular mechanisms by which nuclear receptors interfere with NF-kappaB signalling and quoted the therapeutic implications of their cross-coupling. Strategies that are explored at the moment and that may hold great potential for the future are extensively reviewed.
Laboratory for Eukaryotic Gene Expression and Signal Transduction, Department of Molecular Biology, Ghent University, K.L. Ledeganckstraat 35, 9000 Gent, Belgium.
Valerie
V
Gossye
Guy
G
Haegeman
Karolien
K
De Bosscher
D000818:Animals; D002467:Cell Nucleus / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D018450:Disease Progression; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000502:physiology; D020239:Receptor Cross-Talk / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic
D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear