de Vries Nienke A, Beijnen Jos H, van Tellingen Olaf
Department of Clinical Chemistry, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Hospital), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Cancer Treat Rev. 2009 Dec;35(8):714-23. doi: 10.1016/j.ctrv.2009.08.011. Epub 2009 Sep 19.
High-grade gliomas (WHO grade III anaplastic astrocytoma and grade IV glioblastoma multiforme) are the most common primary tumors in the central nervous system in adults. Unfortunately, despite great efforts in finding better therapies, high-grade glioma remains among the most devastating and deadliest of all human cancers. During recent years, genetic and molecular alterations that underlie this disease have been identified and advanced our basic knowledge about gliomagenesis. Moreover, understanding the molecular biology has also led to the development of genetically engineered mouse models that resemble many of the features of human gliomas. Ideally, such "patient-like" models should be instrumental for preclinical testing of novel therapeutics, but thus far they have not yet been widely implemented for this purpose. This review will discuss the advantages and shortcomings of the established high-grade glioma mouse models with emphasis on their potential applicability for preclinical testing of novel drugs and treatment regimens.
高级别胶质瘤(世界卫生组织III级间变性星形细胞瘤和IV级多形性胶质母细胞瘤)是成人中枢神经系统中最常见的原发性肿瘤。不幸的是,尽管在寻找更好的治疗方法方面付出了巨大努力,但高级别胶质瘤仍然是所有人类癌症中最具破坏性和致命性的癌症之一。近年来,已经确定了构成这种疾病基础的基因和分子改变,并推进了我们对胶质瘤发生的基础知识。此外,对分子生物学的理解也导致了基因工程小鼠模型的发展,这些模型类似于人类胶质瘤的许多特征。理想情况下,这种“类患者”模型应该有助于新型疗法的临床前测试,但到目前为止,它们尚未广泛用于此目的。本综述将讨论已建立的高级别胶质瘤小鼠模型的优缺点,重点是它们在新型药物和治疗方案临床前测试中的潜在适用性。