Molecular Pathways: Revisiting Glycogen Synthase Kinase-3β as a Target for the Treatment of Cancer
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- Amy Walz
- 1Department of Hematology/Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
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- Andrey Ugolkov
- 2Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
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- Sunandana Chandra
- 2Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
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- Alan Kozikowski
- 5Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois.
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- Benedito A. Carneiro
- 2Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
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- Thomas V. O'Halloran
- 3Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois.
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- Francis J. Giles
- 2Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
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- Daniel D. Billadeau
- 6Division of Oncology Research, Schulze Center for Novel Therapeutics, College of Medicine, Mayo Clinic, Rochester, Minnesota.
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- Andrew P. Mazar
- 3Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois.
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説明
<jats:title>Abstract</jats:title> <jats:p>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. Clin Cancer Res; 23(8); 1891–7. ©2017 AACR.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 23 (8), 1891-1897, 2017-04-13
American Association for Cancer Research (AACR)