GSK-3 inhibition overcomes chemoresistance in human breast cancer

• Published in: Cancer letters Vol. 380; no. 2; pp. 384 - 392
• Main Authors: Ugolkov, Andrey, Gaisina, Irina, Zhang, Jin-San, Billadeau, Daniel D, White, Kevin, Kozikowski, Alan, Jain, Sarika, Cristofanilli, Massimo, Giles, Francis, O'Halloran, Thomas, Cryns, Vincent L, Mazar, Andrew P
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.10.2016; Elsevier Limited
• Subjects: 9-ING-41; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antitumor activity; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Camptothecin - analogs & derivatives; Camptothecin - pharmacology; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemoresistance; Dose-Response Relationship, Drug; Drug Design; Drug development; Drug Resistance, Neoplasm - drug effects; Female; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors; Glycogen Synthase Kinase 3 beta - metabolism; GSK-3; Hematology, Oncology and Palliative Medicine; Humans; Immunoglobulins; Indoles - pharmacology; Irinotecan; Kinases; Laboratories; Maleimides - pharmacology; Medical prognosis; Metastases; Metastasis; Mice, Inbred NOD; Mice, SCID; Molecular Targeted Therapy; Patients; Pharmaceutical industry; Protein kinase; Protein Kinase Inhibitors - pharmacology; Protein-serine/threonine kinase; Proteins; Signal Transduction - drug effects; Software; Statistical analysis; Studies; Threonine; Time Factors; Tumor Burden - drug effects; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays; Xenografts; 9-ING-41; good laboratory practice; PKA; drug development; breast cancer; PKC; GSK-3; absorption, distribution, metabolism, excretion, toxicity; GLP; CDK; Akt; ADMET; investigational new drug; chemoresistance; PK; pharmacokinetic; cyclin-dependent kinase; protein kinase A; protein kinase C; IND; protein kinase B; Chemoresistance; Breast cancer; Drug development
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2016.07.006

Highlights • We demonstrate the antitumor effect of GSK-3 inhibition in human breast cancer. • We show that inhibition of GSK-3 can overcome breast cancer chemoresistance. • The GSK-3 inhibitor 9-ING-41 is identified as a candidate agent for breast cancer therapy.