Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Neuro Oncol. 2021 Nov 2;23(23 Suppl 5):S4-S15. doi: 10.1093/neuonc/noab183.
Patients with rare central nervous system (CNS) tumors typically have a poor prognosis and limited therapeutic options. Historically, these cancers have been difficult to study due to small number of patients. Recent technological advances have identified molecular drivers of some of these rare cancers which we can now use to generate representative preclinical models of these diseases. In this review, we outline the advantages and disadvantages of different models, emphasizing the utility of various in vitro and ex vivo models for target discovery and mechanistic inquiry and multiple in vivo models for therapeutic validation. We also highlight recent literature on preclinical model generation and screening approaches for ependymomas, histone mutated high-grade gliomas, and atypical teratoid rhabdoid tumors, all of which are rare CNS cancers that have recently established genetic or epigenetic drivers. These preclinical models are critical to advancing targeted therapeutics for these rare CNS cancers that currently rely on conventional treatments.
患有罕见中枢神经系统 (CNS) 肿瘤的患者通常预后较差，治疗选择有限。这些癌症由于患者数量较少，历史上一直难以研究。最近的技术进步已经确定了其中一些罕见癌症的分子驱动因素，我们现在可以利用这些因素来生成这些疾病的代表性临床前模型。在这篇综述中，我们概述了不同模型的优缺点，强调了各种体外和离体模型在靶点发现和机制研究以及多种体内模型在治疗验证方面的应用。我们还重点介绍了最近关于神经上皮肿瘤、组蛋白突变型高级别神经胶质瘤和非典型畸胎样横纹肌样肿瘤临床前模型生成和筛选方法的文献，这些都是最近确定了遗传或表观遗传驱动因素的罕见 CNS 癌症。这些临床前模型对于推进针对这些罕见 CNS 癌症的靶向治疗至关重要，这些癌症目前依赖于传统治疗方法。
