胶质母细胞瘤中化疗耐药机制的研究进展
Recent Advances in Research on Mechanisms of Chemotherapy Resistance in Glioblastoma
DOI: 10.12677/acm.2026.1682801, PDF,   
作者: 胡陵珊, 陈锦娣*:十堰市太和医院(湖北医药学院附属医院)神经肿瘤疾病诊疗中心,湖北 十堰
关键词: 胶质母细胞瘤;替莫唑胺;耐药机制;Glioblastoma; Temozolomide; Mechanisms of Resistance
摘要: 胶质母细胞瘤(Glioblastoma Multiforme, GBM)恶性程度高,复发率近乎100%。替莫唑胺(Temozolomide, TMZ)是其一线化疗药物,但原发性和获得性耐药严重制约了临床疗效。本文系统归纳了GBM中导致TMZ耐药的演变过程及核心机制,包括:DNA损伤修复通路异常、肿瘤干细胞的固有耐药特性、代谢的重编程、表观遗传紊乱,以及药物外排、凋亡与自噬通路异常。这些机制相互协同,共同构成复杂的耐药调控网络。目前,耐药通路间的交互机制、耐药的动态演变规律以及耐药后的治疗方案仍存在诸多研究空白。未来,借助多组学筛选新型靶点、开展多通路联合靶向治疗、开发新型免疫疗法,有望逆转TMZ耐药,为改善GBM患者预后提供理论依据。
Abstract: Bioblastoma multiforme (GBM) is a highly malignant tumor characterized by a recurrence rate approaching 100%. Temozolomide (TMZ) serves as the first-line chemotherapy agent for GBM; however, both primary and acquired resistance significantly hinder its clinical efficacy. This paper systematically summarizes the evolution and core mechanisms of TMZ resistance in GBM, which include abnormalities in DNA damage repair pathways, intrinsic resistance characteristics of tumor stem cells, metabolic reprogramming, epigenetic dysregulation, and abnormalities in drug efflux, apoptosis, and autophagy pathways. These mechanisms act synergistically to create a complex network that regulates drug resistance. Currently, numerous research gaps persist regarding the interaction mechanisms among resistance pathways, the dynamic evolution of resistance, and post-resistance treatment strategies. In the future, leveraging multi-omics approaches to screen for novel targets, implementing multi-pathway combination targeted therapies, and developing novel immunotherapies may reverse TMZ resistance and provide a theoretical basis for improving the prognosis of GBM patients.
文章引用:胡陵珊, 陈锦娣. 胶质母细胞瘤中化疗耐药机制的研究进展[J]. 临床医学进展, 2026, 16(8): 326-333. https://doi.org/10.12677/acm.2026.1682801

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