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糖原合酶激酶-3(GSK3)抑制剂在癌症治疗中的研究进展。

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

机构信息

School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India.

Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 7):127375. doi: 10.1016/j.ijbiomac.2023.127375. Epub 2023 Oct 13.

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.

摘要

调控癌症发生和发展的复杂分子途径促使人们深入研究新型治疗靶点。糖原合酶激酶-3(GSK3)是一种复杂的丝氨酸/苏氨酸激酶,它在多种细胞过程中发挥着关键作用,包括细胞增殖、分化、凋亡和代谢。利用 GSK3 抑制剂作为癌症治疗的潜在候选药物引起了广泛关注,因为它们能够调节驱动肿瘤发生的关键信号通路。本综述全面探讨了 GSK3 参与癌症进展的分子机制,阐明了它与 Wnt/β-catenin、PI3K/AKT 和 NF-κB 等关键途径的相互作用。通过这些相互作用,GSK3 对肿瘤生长、侵袭、血管生成和转移产生影响,使其成为治疗干预的有吸引力的靶点。讨论包括临床前和临床研究,展示了抑制剂在各种癌症类型中的疗效,包括胰腺癌、卵巢癌、肺癌和其他恶性肿瘤。最近的研究提供了一些见解,强调了将 GSK3 抑制剂与传统化疗药物或靶向治疗联合使用的潜在协同作用,为创新的联合治疗方法开辟了道路。本综述全面概述了围绕 GSK3 抑制剂作为癌症治疗有前途的药物的研究现状。

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