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从信号通路到靶向治疗:揭示胶质母细胞瘤的奥秘并利用二十年进展

英文原题:From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.

PubMed 2023/10/20(内容时间) Signal Transduct Target Ther Q1 · IF 81.2(JCR 2025)

研究概要

胶质母细胞瘤是一种罕见且高度致命的脑癌,在治疗耐药以及成人和儿童患者生存率低方面都带来重大挑战。

中文摘要

胶质母细胞瘤是一种罕见且致死率极高的脑癌,成人和儿童患者均面临治疗耐药及生存率低等重大挑战。尽管脑癌研究因技术革命而不断进步,将对胶质母细胞瘤发病机制的认识转化为临床结局改善,仍是重要的未满足需求。本文重点讨论受体酪氨酸激酶信号通路、表观遗传机制和代谢功能在胶质母细胞瘤发生及治疗耐药中的复杂作用,并综述过去20年来针对这些通路开展靶向治疗的广泛努力。抗体-毒素偶联物或CAR-T细胞疗法等新兴策略通过特异性靶向胶质母细胞瘤细胞表面蛋白,展现潜在价值。将蛋白靶向疗法与免疫疗法结合的策略为未来临床研究带来希望。此外,深入了解胶质母细胞瘤起源细胞对治疗应答的影响,有望推动精准医疗。解决这些挑战对改善患者结局、推进更有效的精准治疗至关重要。

展开英文摘要原文

Glioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms of therapeutic resistance, and poor survival rates for both adult and paediatric patients alike. Despite advancements in brain cancer research driven by a technological revolution, translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need. This review emphasises the intricate role of receptor tyrosine kinase signalling pathways, epigenetic mechanisms, and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance. We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways. Emerging therapeutic approaches, such as antibody-toxin conjugates or CAR T cell therapies, offer potential by specifically targeting proteins on the glioblastoma cell surface. Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research. Moreover, gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches. Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.

论文信息

作者
Dewdney B、Jenkins MR、Best SA、Freytag S、Prasad K、Holst J、Endersby R、Johns TG
单位
Cancer Centre, Telethon Kids Institute, Nedlands, WA, 6009, Australia. brittany.dewdney@telethonkids.org.au.Australia
文献类型
综述 · 非美国政府资助研究
期刊
Signal transduction and targeted therapy2023 Oct 20
原文标识
PubMed 37857607 · DOI 10.1038/s41392-023-01637-8