Department of Pathology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Acta Neuropathol. 2017 Feb;133(2):263-282. doi: 10.1007/s00401-017-1671-4. Epub 2017 Jan 10.
In theory, in vitro and in vivo models for human gliomas have great potential to not only enhance our understanding of glioma biology, but also to facilitate the development of novel treatment strategies for these tumors. For reliable prediction and validation of the effects of different therapeutic modalities, however, glioma models need to comply with specific and more strict demands than other models of cancer, and these demands are directly related to the combination of genetic aberrations and the specific brain micro-environment gliomas grow in. This review starts with a brief introduction on the pathological and molecular characteristics of gliomas, followed by an overview of the models that have been used in the last decades in glioma research. Next, we will discuss how these models may play a role in better understanding glioma development and especially in how they can aid in the design and optimization of novel therapies. The strengths and weaknesses of the different models will be discussed in light of genotypic, phenotypic and metabolic characteristics of human gliomas. The last part of this review provides some examples of how therapy experiments using glioma models can lead to deceptive results when such characteristics are not properly taken into account.
从理论上讲,人类神经胶质瘤的体外和体内模型不仅具有极大的潜力来增进我们对神经胶质瘤生物学的理解,而且还可以促进针对这些肿瘤的新型治疗策略的发展。然而,为了可靠地预测和验证不同治疗方式的效果,神经胶质瘤模型需要符合比其他癌症模型更具体和更严格的要求,这些要求直接与遗传异常和神经胶质瘤在其中生长的特定脑微环境相结合。这篇综述首先简要介绍了神经胶质瘤的病理学和分子特征,然后概述了过去几十年中在神经胶质瘤研究中使用的模型。接下来,我们将讨论这些模型如何在更好地理解神经胶质瘤的发展中发挥作用,特别是它们如何帮助设计和优化新型治疗方法。将根据人类神经胶质瘤的基因型、表型和代谢特征讨论不同模型的优缺点。本综述的最后一部分提供了一些例子,说明了当未适当考虑这些特征时,使用神经胶质瘤模型进行治疗实验可能会导致令人误解的结果。