Abstract
Stat3 is constitutively activated in many human cancers where it functions as a critical mediator of oncogenic signaling through transcriptional activation of genes encoding apoptosis inhibitors (e.g. Bcl-x(L), Mcl-1 and survivin), cell-cycle regulators (e.g. cyclin D1 and c-Myc) and inducers of angiogenesis (e.g. vascular endothelial growth factor). This article reviews several approaches that have been pursued for targeting Stat3 in cancer therapy including antisense strategies, tyrosine kinase inhibition, decoy phosphopeptides, decoy duplex oligonucleotides and G-quartet oligodeoxynucleotides (GQ-ODN). The GQ-ODN strategy is reviewed in somewhat greater detail than the others because it includes a novel system that effectively delivers drug into cells and tissues, addresses successfully the issue of specificity of targeting Stat3 versus Stat1, and has demonstrated efficacy in vivo.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Angiogenesis Inducing Agents / pharmacology
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Animals
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Anticarcinogenic Agents / pharmacology*
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Apoptosis / drug effects*
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Apoptosis / physiology
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Cell Cycle Proteins / pharmacology
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Cell Movement / physiology
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Cell Proliferation
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Humans
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Inhibitor of Apoptosis Proteins / pharmacology
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Ligands
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Neoplasms / drug therapy
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Neoplasms / metabolism*
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Oligonucleotides / pharmacology
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Oligonucleotides, Antisense / pharmacology
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Phosphopeptides / pharmacology
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Plasmids / pharmacology
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Protein Conformation
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Protein Kinase Inhibitors / pharmacology
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Protein-Tyrosine Kinases
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism*
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Signal Transduction / genetics
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Transcriptional Activation / genetics
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Triterpenes / pharmacology
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Tyrphostins / pharmacology
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src Homology Domains / physiology
Substances
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Angiogenesis Inducing Agents
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Anticarcinogenic Agents
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Cell Cycle Proteins
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Inhibitor of Apoptosis Proteins
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Ligands
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Oligonucleotides
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Oligonucleotides, Antisense
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Phosphopeptides
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Protein Kinase Inhibitors
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STAT3 Transcription Factor
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STAT3 protein, human
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Triterpenes
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Tyrphostins
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alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
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Protein-Tyrosine Kinases
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cucurbitacin I