Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution.
Recent evidence indicates a convergence of molecular targets for both prevention and therapy of cancer. Signal-transducer-and-activator-of-transcription-3 (STAT3), a member of a family of six different transcription factors, is closely linked with tumorigenesis. Its role in cancer is indicated by numerous avenues of evidence, including the following: STAT3 is constitutively active in tumor cells; STAT3 is activated by growth factors (e.g., EGF, TGF-alpha, IL-6, hepatocyte growth factor) and oncogenic kinases (e.g., Src); STAT3 regulates the expression of genes that mediate proliferation (e.g., c-myc and cyclin D1), suppress apoptosis (e.g., Bcl-x(L) and survivin), or promote angiogenesis (e.g, VEGF); STAT3 activation has been linked with chemoresistance and radioresistance; and chemopreventive agents have been shown to suppress STAT3 activation. Thus inhibitors of STAT3 activation have potential for both prevention and therapy of cancer. Besides small peptides and oligonucleotides, numerous small molecules have been identified as blockers of STAT3 activation, including synthetic molecules (e.g., AG 490, decoy peptides, and oligonucleotides) and plant polyphenols (e.g., curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, EGCG, and cucurbitacin). This article discusses these aspects of STAT3 in more detail.
Aggarwal
Bharat B
BB
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. aggarwal@mdanderson.org
Sethi
Gautam
G
Ahn
Kwang Seok
KS
Sandur
Santosh K
SK
Pandey
Manoj K
MK
Kunnumakkara
Ajaikumar B
AB
Sung
Bokyung
B
Ichikawa
Haruyo
H
D000818:Animals; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human