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

Abstract

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)–β-catenin destruction complex implies that inhibition of GSK-3 could possibly lead to tumor promotion through the activation of β-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-3β is a critical regulator of nuclear factor (NF)κB nuclear activity, suggesting that inhibition of GSK-3β could be effective in the treatment of a wide variety of tumors with constitutively active NFκB. Herein, the authors will discuss the current understanding of the role of GSK-3 in human cancer and its potential as a therapeutic target.