Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses

Cancer Biol Ther. 2019;20(8):1047-1056. doi: 10.1080/15384047.2019.1595283. Epub 2019 Apr 12.


As a kinase at the crossroads of numerous metabolic and cell growth signaling pathways, glycogen synthase kinase-3 beta (GSK-3β) is a highly desirable therapeutic target in cancer. Despite its involvement in pathways associated with the pathogenesis of several malignancies, no selective GSK-3β inhibitor has been approved for the treatment of cancer. The regulatory role of GSK-3β in apoptosis, cell cycle, DNA repair, tumor growth, invasion, and metastasis reflects the therapeutic relevance of this target and provides the rationale for drug combinations. Emerging data on GSK-3β as a mediator of anticancer immune response also highlight the potential clinical applications of novel selective GSK-3β inhibitors that are entering clinical studies. This manuscript reviews the preclinical and early clinical results with GSK-3β inhibitors and delineates the developmental therapeutics landscape for this potentially important target in cancer therapy.

Keywords: GSK-3β; cancer; clinical trial; immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Immunomodulation / drug effects*
  • Molecular Targeted Therapy* / adverse effects
  • Molecular Targeted Therapy* / methods
  • Neoplasms / drug therapy*
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Organ Specificity
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3 beta