Signal Transduction Inhibitors and Antiangiogenic Therapies for Malignant Glioma
Signal Transduction Inhibitors and Antiangiogenic Therapies for Malignant Glioma
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DOI：
10.1002/glia.21137
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发表时间：
2011-08-01
期刊：
影响因子：
6.2
通讯作者：
Wen, Patrick Y.
中科院分区：
文献类型：
--
作者：
Mellinghoff, Ingo K.;Lassman, Andrew B.;Wen, Patrick Y.
对大量原发性人类胶质母细胞瘤中癌症基因组的详细表征已经确定了反复发生的改变，这些改变导致信号转导途径失调，并且可以用越来越多的小分子药物“用药”。虽然许多这些化合物已在具有类似基因改变的其他人类癌症中显示出临床活性，但迄今为止，胶质母细胞瘤的临床经验令人失望，仅出现罕见且短暂的放射照相反应。我们对耐药性的理解因跨血脑屏障的药物输送的不确定性以及这些肿瘤的生长在多大程度上依赖于任何特定信号通路的知识有限而混淆。这种不确定性至少部分是由于目前评估神经胶质瘤患者信号转导抑制剂的方法存在缺陷，包括在分子上未经选择的患者群体中进行药物测试、肿瘤组织中药物渗透和靶标抑制的记录有限，以及使用可能不是评估这些化合物的最佳放射照相反应标准。 (C) 2011 Wiley-Liss, Inc.
Detailed characterization of the cancer genome in a large number of primary human glioblastomas has identified recurrent alterations that result in deregulation of signal transduction pathways and are "druggable" with a growing number of small molecule pharmaceuticals. While many of these compounds have shown clinical activity in other human cancers harboring similar genetic alterations, the clinical experience in glioblastoma has been disappointing thus far with only rare and transient radiographic responses. Our understanding of drug resistance is confounded by the uncertainty of drug delivery across the blood brain barrier and the limited knowledge to what extent the growth of these tumors depends on any particular signaling pathway. This uncertainty is, at least in part, due to shortcomings in the current approach to evaluate signal transduction inhibitors in glioma patients, including drug testing in molecularly unselected patient populations, limited documentation of drug penetration and target inhibition in tumor tissue, and use of radiographic response criteria that may not be optimal for the evaluation of these compounds. (C) 2011 Wiley-Liss, Inc.