Platelet-derived growth factor receptor alpha in glioma: a bad seed.
Platelet-derived growth factor receptor alpha in glioma: a bad seed.
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DOI：
10.5732/cjc.011.10236
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发表时间：
2011-09
影响因子：
--
通讯作者：
Cheng SY
中科院分区：
文献类型：
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作者：
Liu KW;Hu B;Cheng SY
最近的合作，最常见的和侵略性的脑肿瘤多形性胶质母细胞瘤（GBM）的大规模基因组分析显着推进了我们对这种疾病的理解。编码血小板衍生生长因子受体α（PDGFRα）的基因被鉴定为临床GBM标本中前11个扩增基因中的第三个。PDGFRα信号在正常脑发育过程中的重要作用也暗示了PDGFRα过度激活在胶质瘤中可能的病理后果。尽管使用PDGFR激酶抑制剂的初始临床试验主要令人失望，但涉及基因组分析和个性化药物的诊断和治疗模式有望改善靶向PDGFRα信号传导的治疗。本文综述了PDGFRα信号在正常中枢神经系统（CNS）发育和恶性胶质瘤等病理状态中的作用。我们进一步比较了PDGF诱导的胶质瘤形成的各种动物模型及其作为临床前药物测试的新平台的潜力。然后，我们总结了我们最近的出版物，以及这些发现将如何影响PDGFRα过表达驱动的胶质瘤治疗。通过使用人类或小鼠模型，更好地了解胶质瘤及其微环境中的PDGFRα信号传导，对于设计针对具有异常PDGFRα信号传导的胶质瘤的更有效的治疗策略是必要的。
Recent collaborative, large-scale genomic profiling of the most common and aggressive brain tumor glioblastoma multiforme (GBM) has significantly advanced our understanding of this disease. The gene encoding platelet-derived growth factor receptor alpha (PDGFRα) was identified as the third of the top 11 amplified genes in clinical GBM specimens. The important roles of PDGFRα signaling during normal brain development also implicate the possible pathologic consequences of PDGFRα over-activation in glioma. Although the initial clinical trials using PDGFR kinase inhibitors have been predominantly disappointing, diagnostic and treatment modalities involving genomic profiling and personalized medicine are expected to improve the therapy targeting PDGFRα signaling. In this review, we discuss the roles of PDGFRα signaling during development of the normal central nervous system (CNS) and in pathologic conditions such as malignant glioma. We further compare various animal models of PDGF-induced gliomagenesis and their potential as a novel platform of pre-clinical drug testing. We then summarize our recent publication and how these findings will likely impact treatments for gliomas driven by PDGFRα overexpression. A better understanding of PDGFRα signaling in glioma and their microenvironment, through the use of human or mouse models, is necessary to design a more effective therapeutic strategy against gliomas harboring the aberrant PDGFRα signaling.