Keller Stefanie, Schmidt Mirko H H
Molecular Signal Transduction Laboratories, Institute for Microscopic Anatomy and Neurobiology, Focus Program Translational Neuroscience (FTN), Rhine Mainz Neuroscience Network (rmn2), Johannes Gutenberg University, School of Medicine, 55131 Mainz, Germany.
German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, 55131 Mainz, Germany.
Int J Mol Sci. 2017 Jun 18;18(6):1295. doi: 10.3390/ijms18061295.
Epidermal growth factor receptor (EGFR) and the mutant EGFRvIII are major focal points in current concepts of targeted cancer therapy for glioblastoma multiforme (GBM), the most malignant primary brain tumor. The receptors participate in the key processes of tumor cell invasion and tumor-related angiogenesis and their upregulation correlates with the poor prognosis of glioma patients. Glioma cell invasion and increased angiogenesis share mechanisms of the degradation of the extracellular matrix (ECM) through upregulation of ECM-degrading proteases as well as the activation of aberrant signaling pathways. This review describes the role of EGFR and EGFRvIII in those mechanisms which might offer new combined therapeutic approaches targeting EGFR or EGFRvIII together with drug treatments against proteases of the ECM or downstream signaling to increase the inhibitory effects of mono-therapies.
表皮生长因子受体（EGFR）和突变型EGFRvIII是当前多形性胶质母细胞瘤（GBM）靶向癌症治疗概念中的主要焦点，GBM是最恶性的原发性脑肿瘤。这些受体参与肿瘤细胞侵袭和肿瘤相关血管生成的关键过程，它们的上调与胶质瘤患者的不良预后相关。胶质瘤细胞侵袭和血管生成增加具有共同机制，即通过上调细胞外基质（ECM）降解蛋白酶以及激活异常信号通路来降解ECM。本综述描述了EGFR和EGFRvIII在这些机制中的作用，这可能提供新的联合治疗方法，靶向EGFR或EGFRvIII，同时结合针对ECM蛋白酶或下游信号的药物治疗，以增强单一疗法的抑制效果。
