STAT3 SIGNALING: Anticancer Strategies and Challenges

Table 2

Strategies and Challenges to Therapeutic Intervention into STAT3 Signaling

Strategy Targets Examples Challenges
Inhibit phosphorylation/activation of STAT3 EGFR agonism
TKR activity
JAK activity
SFK activity
Cetuximab, panitumumab
Gefitinib, erlotinib, lapatinib
AG490, LS-104, ICNB1824, CEP-701
Dasatinib, AZD0530, bosutinib
Modest efficacy; development of resistance; myelosuppression, GI toxicity, and adverse events; kinase selectivity and cardiovascular toxicity
Inhibit intermolecular interactions that involve STAT3 STAT3 SH-2 domains Oligopeptides designed from EGFR, gp130, and other receptor or pY-containing peptides; peptide aptamers; G-quartet oligonucleotides; small-molecule peptidomimetics Poor cell permeability and efficacy; poor metabolic stability; poor selectivity for specific SH2 domains; potential for adverse events
Inhibit nuclear import/export of STAT3 Importins α3, α 5, α 7
Importin β
Exportin 1
Karyostatin 1A (effect on STAT3 undetermined)
Leptomycin B and Ratjadone A
Multicomponent nature of nuclear pore and translocation not fully determined; specificity for translocated proteins problematic
Inhibit STAT3-mediated transcription DNA binding site of STAT3 dsODN decoys; peptide aptamers Poor cell permeability without effective and specific delivery systems; poor metabolic stability
Natural products Unspecified Guggulsterone, honokiol, curcumin, resveratrol, flavopiridol, cucurbitacin Specificity, potency, and efficacy, mechanism of action unknown

This Article

  1. MI February 2011 vol. 11 no. 1 18-26