Targeting transcription factors for cancer therapy.
Advances in the molecular biology of oncogenesis have established a key role for transcription factors in malignant transformation. In some cases the activity of the transcription factor itself is altered by mutation. In many other cases, the activity of the transcription factor is affected by mutations in upstream signaling or regulatory proteins. This review highlights four transcription factors--Stat3, Stat5, NF-kappaB, and HIF-1--which are associated with cancer development. The evidence for the involvement of these factors in oncogenesis is reviewed. Further, we examine the efforts to specifically target these transcription factors for therapeutic intervention. Such strategies include using peptidomimetics, antisense oligonucleotides, small molecule inhibitors, and G-quartet oligonucleotides. Inhibition of transcription factor activity may occur at the level of activation, translocation, or DNA binding. Application of these approaches to in vitro and in vivo models of tumorigenesis is discussed.
Redell
Michele S
MS
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Tweardy
David J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D015195:Drug Design; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008894:Milk Proteins / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000187:drug effects; D009687:Nuclear Proteins / Q000187:drug effects / Q000502:physiology; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000502:physiology; D014157:Transcription Factors / Q000187:drug effects* / Q000502:physiology
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008894:Milk Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors