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

摘要

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