TY - JOUR
T1 - Molecular pathways
T2 - Revisiting glycogen synthase kinase-3β as a target for the treatment of cancer
AU - Walz, Amy
AU - Ugolkov, Andrey
AU - Chandra, Sunandana
AU - Kozikowski, Alan
AU - Carneiro, Benedito A.
AU - O'Halloran, Thomas V.
AU - Giles, Francis J.
AU - Billadeau, Daniel D.
AU - Mazar, Andrew P.
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/4/15
Y1 - 2017/4/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-15-2240
DO - 10.1158/1078-0432.CCR-15-2240
M3 - Article
C2 - 28053024
AN - SCOPUS:85018847392
SN - 1078-0432
VL - 23
SP - 1891
EP - 1897
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -
