GBM's multifaceted landscape: highlighting regional and microenvironmental heterogeneity
GBM's multifaceted landscape: highlighting regional and microenvironmental heterogeneity
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DOI：
10.1093/neuonc/nou035
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发表时间：
2014-09-01
期刊：
影响因子：
15.9
通讯作者：
Zadeh, Gelareh
中科院分区：
文献类型：
--
作者：
Vartanian, Alenoush;Singh, Sanjay K.;Zadeh, Gelareh
神经胶质瘤是一组异质性肿瘤，表现出不同的增殖潜力、侵袭性、侵袭性、组织学分级和临床行为。在这篇综述中，我们重点关注多形性胶质母细胞瘤（GBM），这是一种 IV 级胶质瘤，是最常见和恶性的原发性成人脑肿瘤。过去几十年的研究揭示了同级肿瘤之间甚至单个肿瘤内部存在广泛的细胞、分子、遗传、表观遗传和代谢异质性。对不同肿瘤类型的评估表明，具有晚期和临床侵袭性的肿瘤也表现出增强的分子、细胞和微环境异质性。从治疗的角度来看，这种异质性是为患者设计有效治疗策略的主要临床障碍，并对个性化医疗提出了挑战。在这篇综述中，我们将重点介绍 GBM 异质性的关键方面，特别关注区域异质性、缺氧、基因组异质性、肿瘤特异性代谢重编程、新血管形成或血管生成以及基质免疫细胞。我们将进一步讨论 GBM 异质性在治疗中的临床意义。
Gliomas are a heterogeneous group of tumors that show variable proliferative potential, invasiveness, aggressiveness, histological grading, and clinical behavior. In this review, we focus on glioblastoma multiforme (GBM), a grade IV glioma, which is the most common and malignant of primary adult brain tumors. Research over the past several decades has revealed the existence of extensive cellular, molecular, genetic, epigenetic, and metabolic heterogeneity among tumors of the same grade and even within individual tumors. Evaluation of different tumor types has shown that tumors with advanced grade and clinical aggressiveness also display enhanced molecular, cellular, and microenvironmental heterogeneity. From a therapeutic standpoint, this heterogeneity is a major clinical hurdle for devising effective therapeutic strategies for patients and challenges personalized medicine. In this review, we will highlight key aspects of GBM heterogeneity, directing special attention to regional heterogeneity, hypoxia, genomic heterogeneity, tumor-specific metabolic reprogramming, neovascularization or angiogenesis, and stromal immune cells. We will further discuss the clinical implications of GBM heterogeneity in the context of therapy.