文章：

靶向脑癌：恶性胶质瘤和髓母细胞瘤的分子病理学进展

Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma

原文发布日期：2010-05-01

DOI: 10.1038/nrc2818

类型: Review Article

开放获取: 否

要点：

1. Malignant gliomas and medulloblastomas — the most common brain tumours affecting adults and children, respectively — remain responsible for a disproportionate level of morbidity and mortality among cancer patients.
2. The morphological histopathology traditionally used for the subclassification of these brain tumour variants is gradually giving way to more molecularly grounded criteria that better reflect the underlying biology.
3. Recent integrated genomics has further implicated specific molecular networks in the pathogenesis of gliomas and medulloblastomas. These most prominently include receptor tyrosine kinase (RTK) signalling through the Ras–MAPK and PI3K–AKT–mTOR pathways, Wnt signalling and sonic hedgehog (SHH) signalling, along with the cell cycle-regulating RB and p53 pathways.
4. Expression analysis has recently defined transcriptional subclasses for both malignant gliomas and medulloblastomas that seem to be driven by distinct abnormalities in core signalling pathways. Such findings suggest that tumours in a particular molecular subgroup would preferentially respond to different targeted therapies.
5. Malignant gliomas and medulloblastomas also exhibit heterogeneity at the cellular level, with subpopulations of tumour cells harbouring stem-like properties rendering them more resistant to therapy. Such stem-like pools seem to reside in specialized microenvironments that actively maintain their biological characteristics.
6. Treatment challenges posed by malignant gliomas and medulloblastomas remain considerable, and many derive from the molecular and cellular heterogeneity inherent to these tumour variants. They include innate and acquired resistance and the obstacle to effective drug delivery posed by the blood–brain barrier.

要点翻译：

1. 恶性胶质瘤和髓母细胞瘤——分别是影响成人和儿童的最常见脑肿瘤——在癌症患者中导致的发病率和死亡率依然居高不下。
2. 传统上用于这些脑肿瘤亚型分类的形态学组织病理学正逐渐被更基于分子特征的标准所取代，这些标准能更好地反映潜在生物学机制。
3. 近期整合基因组学进一步揭示了胶质瘤和髓母细胞瘤发病机制中特定的分子网络，其中最主要包括通过Ras-MAPK和PI3K-AKT-mTOR通路传导的受体酪氨酸激酶（RTK）信号、Wnt信号和音猬因子（SHH）信号，以及细胞周期调控相关的RB和p53通路。
4. 表达分析最近明确了恶性胶质瘤和髓母细胞瘤的转录亚型，这些亚型似乎由核心信号通路中的不同异常驱动。这些发现表明，特定分子亚型中的肿瘤可能对不同靶向治疗具有优先反应。
5. 恶性胶质瘤和髓母细胞瘤在细胞水平也表现出异质性，具有干细胞特性的肿瘤细胞亚群使其对治疗更具抵抗力。这类干细胞样群体似乎存在于特殊微环境中，这些微环境主动维持着其生物学特性。
6. 恶性胶质瘤和髓母细胞瘤带来的治疗挑战依然巨大，许多挑战源于这些肿瘤变异固有的分子和细胞异质性，包括先天性与获得性耐药，以及血脑屏障对有效药物输送造成的障碍。

英文摘要：

Malignant brain tumours continue to be the cause of a disproportionate level of morbidity and mortality across a wide range of individuals. The most common variants in the adult and paediatric populations — malignant glioma and medulloblastoma, respectively — have been the subject of increasingly intensive research over the past two decades that has led to considerable advances in the understanding of their basic biology and pathogenesis. This Review summarizes these developments in the context of the evolving notion of molecular pathology and discusses the implications that this work has on the design of new treatment regimens.

摘要翻译： 

恶性脑瘤仍是导致各类人群高发病率和高死亡率的重要原因。成人最常见的类型——恶性胶质瘤，以及儿童最常见的类型——髓母细胞瘤，在过去二十年中成为日益深入的研究对象，这些研究极大推动了对它们基本生物学特征及发病机制的理解。本文综述了这些进展，并将其置于不断演进的“分子病理学”概念框架中，进而探讨这一研究对新型治疗方案设计的启示。

原文链接：

Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma