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通过铁代谢推进胶质母细胞瘤治疗:聚焦于转铁蛋白受体 1 和铁死亡创新。

Advancing glioblastoma treatment through iron metabolism: A focus on TfR1 and Ferroptosis innovations.

机构信息

Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Universidad Nacional de Rio Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Río Cuarto X5800BIA, Argentina; Departamento de Patología Animal, Facultad de Agronomía y Veterinaria, Universidad Nacional de Rio Cuarto, Rio Cuarto X5800BIA, Argentina.

Departamento de Biología Molecular, Facultad de Ciencias Exactas, Fisicoquímicas y Naturales, Universidad Nacional de Rio Cuarto, Rio Cuarto X5800BIA, Argentina; Instituto de Biotecnología Ambiental y Salud (INBIAS), Universidad Nacional de Rio Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rio Cuarto X5800BIA, Argentina.

出版信息

Int J Biol Macromol. 2024 Oct;278(Pt 2):134777. doi: 10.1016/j.ijbiomac.2024.134777. Epub 2024 Aug 15.

DOI:10.1016/j.ijbiomac.2024.134777
PMID:39153669
Abstract

Glioblastoma (GBM) represents a formidable challenge in oncology, characterized by aggressive proliferation and poor prognosis. Iron metabolism plays a critical player in GBM progression, with dysregulated iron uptake and utilization contributing to tumor growth and therapeutic resistance. Iron's pivotal role in DNA synthesis, oxidative stress, and angiogenesis underscores its significance in GBM pathogenesis. Elevated expression of iron transporters, such as transferrin receptor 1 (TfR1), highlights the tumor's reliance on iron for survival. Innovative treatment strategies targeting iron dysregulation hold promise for overcoming therapeutic challenges in GBM management. Approaches such as iron chelation therapies, induction of ferroptosis to nanoparticle-based drug delivery systems exploit iron-dependent vulnerabilities, offering avenues for enhance treatment efficacy and improve patient outcomes. As research advances, understanding the complexities of iron-mediated carcinogenesis provides a foundation for developing precision medicine approaches tailored to combat GBM effectively. This review explores the intricate relationship between iron metabolism and GBM, elucidating its multifaceted implications and therapeutic opportunities. By consolidating the latest insights into iron metabolism in GBM, this review underscores its potential as a therapeutic target for improving patient care in combination with the standard of care approach.

摘要

胶质母细胞瘤(GBM)是肿瘤学领域的一大挑战,其特征为侵袭性增殖和预后不良。铁代谢在 GBM 进展中起着关键作用,铁摄取和利用的失调导致肿瘤生长和治疗耐药。铁在 DNA 合成、氧化应激和血管生成中的关键作用突显了其在 GBM 发病机制中的重要性。铁转运蛋白,如转铁蛋白受体 1(TfR1)的高表达,突出了肿瘤对铁的生存依赖。针对铁失调的创新治疗策略有望克服 GBM 管理中的治疗挑战。铁螯合疗法、诱导铁死亡等纳米药物递送系统利用铁依赖性脆弱性,为提高治疗效果和改善患者预后提供了途径。随着研究的进展,理解铁介导的致癌作用的复杂性为开发针对 GBM 的精准医学方法提供了基础,以有效地进行治疗。本综述探讨了铁代谢与 GBM 之间的复杂关系,阐明了其多方面的影响和治疗机会。通过整合 GBM 中铁代谢的最新见解,本综述强调了其作为治疗靶点的潜力,可与标准治疗方法相结合,改善患者治疗效果。

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