Molecular pathways: Revisiting glycogen synthase kinase-3β as a target for the treatment of cancer

Amy Walz, Andrey Ugolkov, Sunandana Chandra, Alan Kozikowski, Benedito A. Carneiro, Thomas V. O'Halloran, Francis J. Giles, Daniel D. Billadeau, Andrew P Mazar*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, is a complex regulator of numerous cellular functions. GSK-3β is a unique kinase which is constitutively active in resting and nonstimulated cells. GSK-3β has been implicated in a wide range of diseases including neurodegeneration, inflammation and fibrosis, noninsulin-dependent diabetes mellitus, and cancer. It is a regulator of NF-κB-mediated survival of cancer cells, which provided a rationale for the development of GSK-3 inhibitors targeting malignant tumors. Recent studies, many of them reported over the past decade, have identified GSK-3β as a potential therapeutic target in more than 15 different types of cancer. Whereas only active GSK-3β is expressed in cancer cell nucleus, aberrant nuclear accumulation of GSK-3β has been identified as a hallmark of cancer cells in malignant tumors of different origin. This review focuses on the preclinical and clinical development of GSK-3 inhibitors and the potential therapeutic impact of targeting GSK-3β in human cancer.

Original languageEnglish (US)
Pages (from-to)1891-1897
Number of pages7
JournalClinical Cancer Research
Volume23
Issue number8
DOIs
StatePublished - Apr 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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