Targeting GSK-3: a promising approach for cancer therapy?

Future Oncol. 2006 Feb;2(1):91-100. doi: 10.2217/14796694.2.1.91.


Glycogen synthase kinase (GSK)-3 has emerged as one of the most attractive therapeutic targets for the treatment of multiple neurological diseases, including Alzheimer's, stroke and bipolar disorders, as well as noninsulin-dependent diabetes mellitus and inflammation. Although the prominent role of GSK-3 in the adenomatous polyposis coli (APC)-beta-catenin destruction complex implies that inhibition of GSK-3 could possibly lead to tumor promotion through the activation of beta-catenin, several recent studies have shed new light on the activity of GSK-3 in cancer and provide insight into the molecular mechanisms by which it regulates tumor cell proliferation and survival of multiple human malignancies. In fact, GSK-3beta is a critical regulator of nuclear factor (NF)kappaB nuclear activity, suggesting that inhibition of GSK-3beta could be effective in the treatment of a wide variety of tumors with constitutively active NFkappaB. Herein, the authors will discuss the current understanding of the role of GSK-3 in human cancer and its potential as a therapeutic target.

Publication types

  • Review

MeSH terms

  • Carbohydrates / physiology
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor Proteins / pharmacology
  • Drug Design*
  • Glycogen Synthase Kinase 3 / analysis
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / pharmacology
  • Humans
  • NF-kappa B / antagonists & inhibitors
  • Neoplasms / chemistry
  • Neoplasms / drug therapy*


  • Carbohydrates
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • NF-kappa B
  • Glycogen Synthase Kinase 3