揭开雌激素受体的神秘面纱:从结构上洞察治疗胶质母细胞瘤的激动剂和拮抗剂。

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Asokan Madeshwaran, Periyasamy Vijayalakshmi, Vidhya Rekha Umapathy, Rajeshkumar Shanmugam, Chandrabose Selvaraj
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引用次数: 0

摘要

胶质母细胞瘤(GBM)是一种起源于胶质细胞的恶性脑肿瘤,是最常见的原发性脑恶性肿瘤之一,每十万人中就有一人受其影响,通常发生在额叶。雌激素(如雌二醇-17(E2))对 GBM 的发展、转移和血管生成有显著影响。雌激素受体(ER)在信号转导和生理学中至关重要,因此是潜在的治疗靶点。然而,它们在 GBM 发病机制中的作用仍不清楚。本综述探讨了 GBM 中的雌激素受体,重点关注它们在肿瘤免疫逃避、肿瘤微环境调控和 GBM 进展机制中的参与。此外,还讨论了针对ERs治疗GBM的治疗机会。雌激素主要由卵巢合成,少量由肾上腺和脂肪组织合成,调节生殖系统、骨密度、皮肤健康和心血管功能。GBM的侵袭性和异质性使治疗方法的开发变得复杂。临床前研究结果表明,使用激素受体激动剂或拮抗剂进行内分泌治疗可以延长患者的生存期并改善治疗后的生活质量。ERβ通路尤其具有抑制肿瘤的潜力,可限制胶质瘤的发展,且副作用较小。ERβ激动剂可能成为治疗脑胶质瘤的一类新型药物。确定生物标志物和特异性治疗靶点对于早期检测和改善预后至关重要。雌激素及其受体能调节多种生物过程,能穿透血脑屏障,能控制基因组和非基因组的转录,因此是治疗 GBM 的有利靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unlocking estrogen receptor: Structural insights into agonists and antagonists for glioblastoma therapy.

Glioblastoma (GBM), a malignant brain tumor originating in glial cells, is one of the most common primary brain malignancies, affecting one in 100,000 people, typically in the frontal lobe. Estrogens, like estradiol-17 (E2), significantly influence GBM progression, metastasis, and angiogenesis. Estrogen receptors (ERs) are crucial in signal transduction and physiology, making them potential therapeutic targets. However, their roles in GBM pathogenesis remain unclear. This review explores ERs in GBM, focusing on their involvement in tumor immune evasion, modulation of the tumor microenvironment, and the mechanisms underlying GBM progression. Additionally, therapeutic opportunities targeting ERs for GBM treatment are discussed. Estrogen, synthesized primarily in ovaries and in smaller amounts by adrenal glands and fat tissues, regulates reproductive systems, bone density, skin health, and cardiovascular function. The invasive nature and heterogeneity of GBM complicate therapy development. Preclinical findings suggest that endocrine therapy with hormone receptor agonists or antagonists can extend patient survival and improve post-treatment quality of life. The ERβ pathway, in particular, shows tumor-suppressive potential, limiting glioma progression with fewer side effects. ERβ agonists could become a novel drug class for GBM treatment. Identifying biomarkers and specific therapeutic targets is crucial for early detection and improved prognosis. Estrogen and its receptors are advantageous for GBM treatment due to their regulation of numerous biological processes, ability to penetrate the blood-brain barrier, and genomic and non-genomic control of transcription, making them promising targets for GBM therapy.

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来源期刊
Advances in protein chemistry and structural biology
Advances in protein chemistry and structural biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
7.40
自引率
0.00%
发文量
66
审稿时长
>12 weeks
期刊介绍: Published continuously since 1944, The Advances in Protein Chemistry and Structural Biology series has been the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins. Each thematically organized volume is guest edited by leading experts in a broad range of protein-related topics.
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