Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, Boston, MA 02129, USA
Neuroscience Program, Harvard Medical School, Boston MA 02129, USA
Cells. 2019 Sep 30;8(10):1177. doi: 10.3390/cells8101177.
Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults associated with a poor survival. Current standard of care consists of surgical resection followed by radiation and chemotherapy. GBMs are highly heterogeneous, having a complex interaction among different cells within the tumor as well as the tumor microenvironment. One of the main challenges in the neuro-oncology field in general, and GBM in particular, is to find an optimum culture condition that maintains the molecular genotype and phenotype as well as heterogeneity of the original tumor in vitro and in vivo. Established cell lines were shown to be a poor model of the disease, failing to recapitulate the phenotype and harboring non-parental genotypic mutations. Given the growing understanding of GBM biology, the discovery of glioma cancer stem-like cells (GSCs), and their role in tumor formation and therapeutic resistance, scientists are turning more towards patient-derived cells and xenografts as a more representative model. In this review, we will discuss the current state of patient-derived GSCs and their xenografts; and provide an overview of different established models to study GBM biology and to identify novel therapeutics in the pre-clinical phase.
胶质母细胞瘤（GBM）是成人中最常见且恶性程度最高的原发性脑肿瘤，患者的生存率较低。目前的治疗标准包括手术切除，然后进行放疗和化疗。GBM 具有高度异质性，肿瘤内不同细胞以及肿瘤微环境之间存在复杂的相互作用。神经肿瘤学领域，尤其是 GBM 领域的主要挑战之一是找到一种最佳的培养条件，以在体外和体内保持原始肿瘤的分子基因型和表型以及异质性。已建立的细胞系被证明是疾病的不良模型，无法重现表型，并且存在非亲本基因型突变。鉴于对 GBM 生物学的认识不断加深，发现了胶质瘤类癌干细胞（GSCs）及其在肿瘤形成和治疗耐药性中的作用，科学家们越来越倾向于使用患者来源的细胞和异种移植物作为更具代表性的模型。在这篇综述中，我们将讨论当前的患者来源 GSCs 及其异种移植物的状态，并概述用于研究 GBM 生物学和在临床前阶段确定新疗法的不同已建立模型。
