University of Tennessee Health Science Center , Department of Clinical Pharmacy , 19 S. Manassas, Memphis, TN, 39103 , USA +901 448 1136 ; +901 448 6064 ;
Expert Opin Drug Discov. 2011 Dec;6(12):1271-83. doi: 10.1517/17460441.2011.632628. Epub 2011 Oct 28.
High-grade gliomas are among the most deadly of all cancer types and are also the most common malignant primary tumors of the CNS. Large-scale studies that have analyzed the transcriptional and translational expression patterns of glioma have found that the majority of these tumors can be categorized based on specific genomic anomalies. Genetically engineered mouse models (GEMMs) that represent the molecular subgroups of the human disease harbor a variety of molecular alterations that have been proven to drive gliomagenesis. These models provide an opportunity to assess the effects of novel therapies in the presence of specific molecular defects. Research using GEMMs, which are associated with these subclasses, allow researchers to assess drug efficacy by subclass.
In this review, the authors discuss the histological and molecular characteristics of malignant gliomas, the therapies used to treat them and the animal models that closely recapitulate them.
It is likely that GEMMs that recapitulate the molecular character of human tumors will provide a more accurate prediction of individuals who may be more or less likely to benefit from specific therapies. This knowledge can be then used to drive clinical trial design and this, in turn, could lead to better therapeutic outcomes.
高级别神经胶质瘤是所有癌症类型中最致命的一种,也是中枢神经系统最常见的恶性原发性肿瘤。对分析胶质瘤转录和翻译表达模式的大规模研究发现,这些肿瘤中的大多数可以根据特定的基因组异常进行分类。代表人类疾病分子亚群的基因工程小鼠模型(GEMM)具有多种已被证明可驱动神经胶质瘤发生的分子改变。这些模型为评估特定分子缺陷存在下的新型治疗方法提供了机会。使用与这些亚类相关的 GEMM 进行研究,使研究人员能够通过亚类评估药物的疗效。
在这篇综述中,作者讨论了恶性神经胶质瘤的组织学和分子特征、用于治疗它们的疗法以及能够很好地再现这些特征的动物模型。
很可能能够再现人类肿瘤分子特征的 GEMM 将更准确地预测哪些个体更有可能或不太可能从特定治疗中获益。然后可以利用这些知识来指导临床试验设计,从而提高治疗效果。