PMID- 21568920
OWN - NLM
STAT- MEDLINE
DA  - 20110608
DCOM- 20111017
IS  - 1875-533X (Electronic)
IS  - 0929-8673 (Linking)
VI  - 18
IP  - 16
DP  - 2011
TI  - STAT-3 inhibitors: state of the art and new horizons for cancer treatment.
PG  - 2359-75
AB  - The signal transducers and activators of transcription (STATs) include a class of
      cytoplasmic signaling proteins whose role in the regulation of cell growth and
      survival is mediated by phosphorylation of a critical tyrosine residue within the
      STAT protein. This occurs in response to cytokines and growth factors modulating 
      the expression of specific target genes. In particular, phosphorylation induces
      STAT:STAT dimer formation between two monomers, via reciprocal phosphoTyr
      (pTyr)-SH2 domain interactions. To date, seven members of the STAT family, all
      with different roles, have been identified in mammals. After dimerization,
      phosphorylated STATs enter the nucleus and, working co-ordinately with other
      transcriptional co-activators and transcription factors, induce increased
      transcriptional initiation. In healthy human and animal cells, ligand-dependent
      activation of STATs is a transient process, lasting for several minutes to
      several hours. In contrast, in many cancerous cell lines and tumors, where growth
      factor dysregulation is frequently at the heart of cellular transformation, the
      STAT proteins (in particular STAT1, 3 and 5) are persistently
      tyrosine-phosphorylated or activated; abnormal levels of STAT3 activation have
      been observed in breast, ovarian, prostate, hematological and head and neck
      cancer cell lines. Thus, in this review, we examine the most important classes of
      agents designed to disrupt STAT3 signaling, with particular regard to STAT3
      dimerization inhibitors, which could play a significant role in the future of
      cancer and adjuvant cancer therapies.
AD  - Dipartimento di Chimica Farmaceutica e Tossicologica, "ldquoDrug Discover"
      Laboratory Universita di Napoli "Federico II", Facolta di Farmacia, via D.
      Montesano 49, 1-80131 Napoli, Italy. lavecchi@unina.it
FAU - Lavecchia, A
AU  - Lavecchia A
FAU - Di Giovanni, C
AU  - Di Giovanni C
FAU - Novellino, E
AU  - Novellino E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Organic Chemicals)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Peptides)
RN  - 0 (STAT3 Transcription Factor)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Neoplasms/*drug therapy/metabolism/pathology
MH  - Organic Chemicals/chemical synthesis/chemistry/*pharmacology
MH  - Organometallic Compounds/chemical synthesis/chemistry/*pharmacology
MH  - Peptides/chemical synthesis/chemistry/*pharmacology
MH  - STAT3 Transcription Factor/*antagonists & inhibitors/chemistry/metabolism
MH  - Signal Transduction/drug effects
EDAT- 2011/05/17 06:00
MHDA- 2011/10/18 06:00
CRDT- 2011/05/17 06:00
PHST- 2011/02/05 [received]
PHST- 2011/05/08 [accepted]
AID - BSP/CMC/E-Pub/2011/ 168 [pii]
PST - ppublish
SO  - Curr Med Chem. 2011;18(16):2359-75.