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Molecular Pathways: Revisiting Glycogen Synthase Kinase-3? as a target for the treatment of cancer #MMPMID28053024
Clin Cancer Res 2017[Apr]; 23 (8): 1891-7 PMID28053024show ga
Glycogen synthase kinase-3? (GSK-3?), a serine/threonine protein kinase, is a complex regulator of numerous cellular functions. GSK-3? is a unique kinase which is constitutively active in resting and non-stimulated cells. GSK-3? 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-?B-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-3? as a potential therapeutic target in at over 15 different types of cancer. Whereas only active GSK-3? is expressed in cancer cell nucleus, aberrant nuclear accumulation of GSK-3? 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-3? in human cancer.