Preclinical models of meningioma: Cell culture and animal systems.

Preclinical models of meningioma: Cell culture and animal systems.
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DOI:
10.1016/b978-0-12-804280-9.00008-1
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发表时间:
2020-01-01
影响因子:
--
通讯作者:
Raleigh, David R
Raleigh, David R
中科院分区:
其他
文献类型:
--
作者:
Choudhury, Abrar;Raleigh, David R

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脑膜瘤是最常见的原发性颅内肿瘤,但目前尚无有效的系统或分子治疗方法。理解脑膜瘤生物学和确定新的治疗靶点的主要障碍之一是缺乏易处理的临床前模型。虽然已经为脑膜瘤创建了许多模型系统,但许多都有根本性的缺点。本章详细介绍了现有脑膜瘤模型的优势和局限性,并提出了未来可能的模型系统。细胞培养脑膜瘤模型由来自肿瘤切除标本的人脑膜瘤细胞系组成,但不幸的是,体外系统不能捕获脑膜瘤的组织学结构、肿瘤微环境或异质性。小鼠脑膜瘤系统的范围从基因工程小鼠模型(GEMM)到患者来源的异种移植物(PDX),并克服了培养脑膜瘤细胞的一些局限性。然而,许多体内系统的可重复性差,或未能概括脑膜瘤生物学的重要方面,如肿瘤潜伏期。尽管存在这些缺点,脑膜瘤生物学的新发现和用于开发模型系统的技术的进步为在不久的将来开发出更具代表性的脑膜瘤模型提供了希望。
Meningioma is the most common primary intracranial tumor; yet there are no effective systemic or molecular therapies for meningioma patients. One of the primary barriers to understanding meningioma biology and identifying novel therapeutic targets is the lack of tractable preclinical models. While numerous model systems have been created for meningioma, many have fundamental drawbacks. This chapter details the strengths and limitations of existing meningioma models and suggests possible future model systems. Cell culture meningioma models consist of human meningioma cell lines derived from tumor resection specimens, but unfortunately, in vitro systems do not capture the histologic architecture, the tumor microenvironment, or the heterogeneity of meningiomas. Mouse meningioma systems range from genetically engineered mouse models (GEMMs) to patient-derived xenografts (PDXs) and overcome some of the limitations of cultured meningioma cells. However, many in vivo systems have poor reproducibility or fail to recapitulate important aspects of meningioma biology, such as tumor latency. Despite these drawbacks, new discoveries in meningioma biology and advances in the technologies used to develop model systems provide hope that more representative models of meningioma will be developed in the near future.