Department of Neurosurgery, University of Ulm Medical School, Steinhövelstr 9, D-89075 Ulm, Germany.
Molecules. 2010 Jun 30;15(7):4670-8. doi: 10.3390/molecules15074670.
The epidermal growth factor receptor (HER1/EGFR) is known to be disregulated in a large subgroup of glioblastoma multiforme cases. Disregulation of HER1/EGFR is related to malignant transformation and tumor growth in various human cancers, including malignant glioma. One mechanism that may lead to disregulated HER1/EGFR signaling is the intrinsic alteration of the receptor structure due to mutational changes. The most common mutant form of HER1/EGFR, named variant III (EGFRvIII), results from an 801 bp in-frame deletion in the DNA sequence encoding the extracellular ligand-binding domain. Independent of ligand-binding, EGFRvIII is constitutively activated and beyond external control. Since its cellular expression was shown to relate enhanced tumorigenicity, various therapeutic strategies were developed to target EGFRvIII, including monoclonal antibodies, vaccination therapies and small-molecule tyrosine kinase inhibitors. In this review, we focus on ribozyme-mediated inhibition of EGFRvIII messenger RNA expression as a gene therapeutic approach for EGFRvIII-expressing glioblastoma multiforme.
表皮生长因子受体（HER1/EGFR）在很大一部分多形性胶质母细胞瘤病例中被发现失调。HER1/EGFR 的失调与多种人类癌症（包括恶性神经胶质瘤）的恶性转化和肿瘤生长有关。导致 HER1/EGFR 信号失调的一种机制可能是由于受体结构的内在改变，导致受体结构的突变改变。HER1/EGFR 的最常见突变形式，命名为变体 III（EGFRvIII），是由于 DNA 序列中外源配体结合域编码区的 801bp 框内缺失而产生的。与配体结合无关，EGFRvIII 是组成性激活的，不受外部控制。由于其细胞表达与增强的肿瘤发生有关，因此开发了各种针对 EGFRvIII 的治疗策略，包括单克隆抗体、疫苗治疗和小分子酪氨酸激酶抑制剂。在这篇综述中，我们重点介绍了核酶介导的 EGFRvIII 信使 RNA 表达抑制作为针对表达 EGFRvIII 的多形性胶质母细胞瘤的基因治疗方法。
