Wainwright Derek A, Horbinski Craig M, Hashizume Rintaro, James C David
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Neurotherapeutics. 2017 Apr;14(2):385-392. doi: 10.1007/s13311-017-0523-1.
The development and application of rodent models for preclinical testing of novel therapeutics and approaches for treating brain tumors has been a mainstay of neuro-oncology preclinical research for decades, and is likely to remain so into the foreseeable future. These models serve as an important point of entry for analyzing the potential efficacy of experimental therapies that are being considered for clinical trial evaluation. Although rodent brain tumor models have seen substantial change, particularly since the introduction of genetically engineered mouse models, certain principles associated with the use of these models for therapeutic testing are enduring, and form the basis for this review. Here we discuss the most common rodent brain tumor models while directing specific attention to their usefulness in preclinical evaluation of experimental therapies. These models include genetically engineered mice that spontaneously or inducibly develop brain tumors; syngeneic rodent models in which cultured tumor cells are engrafted into the same strain of rodent from which they were derived; and patient-derived xenograft models in which human tumor cells are engrafted in immunocompromised rodents. The emphasis of this review is directed to the latter.
几十年来,用于新型脑肿瘤治疗药物和方法临床前测试的啮齿动物模型的开发与应用一直是神经肿瘤学临床前研究的支柱,并且在可预见的未来可能仍将如此。这些模型是分析正在考虑进行临床试验评估的实验性疗法潜在疗效的重要切入点。尽管啮齿动物脑肿瘤模型已经发生了重大变化,尤其是自基因工程小鼠模型引入以来,但与使用这些模型进行治疗测试相关的某些原则依然适用,并构成了本综述的基础。在此,我们将讨论最常见的啮齿动物脑肿瘤模型,同时特别关注它们在实验性疗法临床前评估中的实用性。这些模型包括自发或诱导性发生脑肿瘤的基因工程小鼠;将培养的肿瘤细胞移植到其来源的同一品系啮齿动物体内的同基因啮齿动物模型;以及将人类肿瘤细胞移植到免疫缺陷啮齿动物体内的患者来源异种移植模型。本综述的重点是后者。