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巨噬细胞迁移抑制因子作为神经肿瘤学的治疗靶点:综述

Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review.

作者信息

Jarmula Jakub, Lee Juyeun, Lauko Adam, Rajappa Prajwal, Grabowski Matthew M, Dhawan Andrew, Chen Peiwen, Bucala Richard, Vogelbaum Michael A, Lathia Justin D

机构信息

Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

出版信息

Neurooncol Adv. 2024 Aug 10;6(1):vdae142. doi: 10.1093/noajnl/vdae142. eCollection 2024 Jan-Dec.

Abstract

Primary central nervous system (CNS) tumors affect tens of thousands of patients each year, and there is a significant need for new treatments. Macrophage migration inhibitory factor (MIF) is a cytokine implicated in multiple tumorigenic processes such as cell proliferation, vascularization, and immune evasion and is therefore a promising therapeutic target in primary CNS tumors. There are several MIF-directed treatments available, including small-molecule inhibitors, peptide drugs, and monoclonal antibodies. However, only a small number of these drugs have been tested in preclinical models of primary CNS tumors, and even fewer have been studied in patients. Moreover, the brain has unique therapeutic requirements that further make effective targeting challenging. In this review, we summarize the latest functions of MIF in primary CNS tumor initiation and progression. We also discuss advances in MIF therapeutic development and ongoing preclinical studies and clinical trials. Finally, we discuss potential future MIF therapies and the strategies required for successful clinical translation.

摘要

原发性中枢神经系统(CNS)肿瘤每年影响数以万计的患者,因此迫切需要新的治疗方法。巨噬细胞迁移抑制因子(MIF)是一种细胞因子,参与多种肿瘤发生过程,如细胞增殖、血管生成和免疫逃逸,因此是原发性CNS肿瘤中一个有前景的治疗靶点。目前有几种针对MIF的治疗方法,包括小分子抑制剂、肽类药物和单克隆抗体。然而,这些药物中只有少数在原发性CNS肿瘤的临床前模型中进行了测试,在患者中进行研究的更少。此外,大脑有独特的治疗需求,这进一步增加了有效靶向治疗的挑战性。在这篇综述中,我们总结了MIF在原发性CNS肿瘤起始和进展中的最新功能。我们还讨论了MIF治疗开发的进展以及正在进行的临床前研究和临床试验。最后,我们讨论了未来潜在的MIF治疗方法以及成功进行临床转化所需的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a59/11372298/c2b86656914a/vdae142_fig1.jpg

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