title: Molecular Pathways: Revisiting Glycogen Synthase Kinase-3β as a Target for the Treatment of Cancer.
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.Clin Cancer Res; 23(8); 1891-7. ©2017 AACR.
authors.affiliation: Department of Hematology/Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.|Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Amy
authors.initials: A
authors.lastname: Walz
authors.affiliation: Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.|Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois.
authors.forename: Andrey
authors.initials: A
authors.lastname: Ugolkov
authors.affiliation: Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.
authors.forename: Sunandana
authors.initials: S
authors.lastname: Chandra
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Alan
authors.initials: A
authors.lastname: Kozikowski
authors.affiliation: Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.
authors.forename: Benedito A
authors.initials: BA
authors.lastname: Carneiro
authors.affiliation: Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: O'Halloran
authors.affiliation: Developmental Therapeutic Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.affiliation: Division of Oncology Research, Schulze Center for Novel Therapeutics, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeau
authors.affiliation: Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois. mazar@monopartherapeutics.com.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.|Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.|Monopar Therapeutics, Inc., Northbrook, Illinois.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Mazar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000071679:Glycogen Synthase Kinase 3 beta