A review of Glycogen Synthase Kinase-3 (GSK3) inhibitors for cancers therapies

Abstract

The intricate molecular pathways governing cancer development and progression have spurred intensive investigations into novel therapeutic targets. Glycogen Synthase Kinase-3 (GSK3), a complex serine/threonine kinase, has emerged as a key player with intricate roles in various cellular processes, including cell proliferation, differentiation, apoptosis, and metabolism. Harnessing GSK3 inhibitors as potential candidates for cancer therapy has garnered significant interest due to their ability to modulate key signalling pathways that drive oncogenesis. The review encompasses a thorough examination of the molecular mechanisms underlying GSK3's involvement in cancer progression, shedding light on its interaction with critical pathways such as Wnt/β-catenin, PI3K/AKT, and NF-κB. Through these interactions, GSK3 exerts influence over tumour growth, invasion, angiogenesis, and metastasis, rendering it an attractive target for therapeutic intervention. The discussion includes preclinical and clinical studies, showcasing the inhibitors efficacy across a spectrum of cancer types, including pancreatic, ovarian, lung, and other malignancies. Insights from recent studies highlight the potential synergistic effects of combining GSK3 inhibitors with conventional chemotherapeutic agents or targeted therapies, opening avenues for innovative combinatorial approaches. This review provides a comprehensive overview of the current state of research surrounding GSK3 inhibitors as promising agents for cancer treatment.

Keywords: GSK3; Inflammation; Inhibitors; Lung cancer; Renal cancer; Thyroid cancer.