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Molecular Pathways: Revisiting Glycogen Synthase Kinase-3? as a Target for the
Treatment of Cancer
#MMPMID28053024
Walz A
; Ugolkov A
; Chandra S
; Kozikowski A
; Carneiro BA
; O'Halloran TV
; Giles FJ
; Billadeau DD
; Mazar AP
Clin Cancer Res
2017[Apr]; 23
(8
): 1891-1897
PMID28053024
show 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 nonstimulated 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 more than 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. Clin Cancer Res; 23(8); 1891-7. ©2017 AACR.
|Animals
[MESH]|Antineoplastic Agents/pharmacology
[MESH]|Glycogen Synthase Kinase 3 beta/*antagonists & inhibitors
[MESH]|Humans
[MESH]|Molecular Targeted Therapy/*methods
[MESH]|Neoplasms/drug therapy/*enzymology
[MESH]
 
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