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

Research output: Contribution to journalArticlepeer-review

58 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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