摘要
成胶质瘤细胞(GBM)是一个死亡性脑瘤,目前所以企图控制它的方法都失败了。然而,它的未来是有希望的,因为我现在了解到癌症基因组图谱项目中GBM的分子景观。GBMs表达出明显的肿瘤间或肿瘤内的不均匀,为了控制这种肿瘤需要一个个体化的方法。一个在大量GBMs中基因扩增和突变的靶点是表皮生长因子受体(EGFR),但是未能成功靶向这个受体。我们把这个失败归因于GBM中EGFR的分子不均匀性以及先前测试的EGFR络氨酸激酶抑制剂较差的大脑渗透能力。本文讨论了EGFR分子不均匀性,为测试AZD9291、三分之代、具有高亲和力和优秀大脑渗透的不可逆EGFE-TKI提供了一个合理的临床前和临床向导。
关键词: 成胶质瘤细胞,EGFR,异质性,靶向,治疗,TCGA
图形摘要
Current Cancer Drug Targets
Title:A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma
Volume: 17 Issue: 3
关键词: 成胶质瘤细胞,EGFR,异质性,靶向,治疗,TCGA
摘要: Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit significant inter- and intratumoral heterogeneity, and to control this type of tumor, a personalized approach is required. One target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But all attempts to target it have been unsuccessful. We attribute the reason for this failure to the molecular heterogeneity of EGFR in GBM, as well as to the poor brain penetration of previously tested EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs). In this review, we discuss the molecular heterogeneity of EGFR and provide rational preclinical and clinical guidelines for testing AZD9291, a third generation, irreversible EGFR-TKI with both a high affinity for EGFRvIII and excellent brain penetration.
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Cite this article as:
A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma, Current Cancer Drug Targets 2017; 17 (3) . https://dx.doi.org/10.2174/1568009616666161227091522
DOI https://dx.doi.org/10.2174/1568009616666161227091522 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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