Epidermal Growth Factor Receptor in Glioma: Signal Transduction, Neuropathology, Imaging, and Radioresistance
Epidermal Growth Factor Receptor in Glioma: Signal Transduction, Neuropathology, Imaging, and Radioresistance
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DOI：
10.1593/neo.10688
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发表时间：
2010-09-01
期刊：
影响因子：
4.8
通讯作者：
Habib, Amyn A.
中科院分区：
文献类型：
--
作者：
Hatanpaa, Kimmo J.;Burma, Sandeep;Habib, Amyn A.
表皮生长因子受体 (EGFR) 信号传导异常在癌症中很常见。野生型和突变型 EGFR 表达增加是多种癌症的普遍特征。几十年来，癌症中的 EGFR 信号传导一直是深入研究的焦点，主要有两个原因。首先，异常的 EGFR 信号传导可能在癌症的发病机制中发挥重要作用，因此 EGFR 介导的致癌信号传导机制引起人们的兴趣。其次，EGFR 信号系统是治疗干预的一个有吸引力的目标。 EGFR 基因扩增和过度表达是胶质母细胞瘤 (GBM) 的一个特别显着的特征，在大约 40% 的肿瘤中观察到。 GBM是成人中枢神经系统最常见的原发性恶性肿瘤。在大约 50% 具有 EGFR 扩增的肿瘤中，可以检测到特定的 EGFR 突变体（EGFRvIII，也称为 EGFR III 型、de2-7、Delta EGFR）。该突变体具有高度致癌性，由 EGFR 基因的外显子 2 至 7 缺失产生，导致受体胞外域的 267 个氨基酸框内缺失。 EGFRvIII 无法结合配体，并且它发出组成型信号。尽管 EGFRvIII 具有与野生型受体相同的信号传导结构域，但它似乎产生一组独特的下游信号，可能有助于增加致瘤性。在这篇综述中，我们讨论了 GBM 中 EGFR 信号传导关键方面的最新进展，重点关注神经病理学、信号转导、EGFR 成像以及 EGFR 在介导 GBM 放射治疗耐药中的作用。
Aberrant epidermal growth factor receptor (EGFR) signaling is common in cancer. Increased expression of wild type and mutant EGFR is a widespread feature of diverse types of cancer. EGFR signaling in cancer has been the focus of intense investigation for decades primarily for two reasons. First, aberrant EGFR signaling is likely to play an important role in the pathogenesis of cancer, and therefore, the mechanisms of EGFR-mediated oncogenic signaling are of interest. Second, the EGFR signaling system is an attractive target for therapeutic intervention. EGFR gene amplification and overexpression are a particularly striking feature of glioblastoma (GBM), observed in approximately 40% of tumors. GBM is the most common primary malignant tumor of the central nervous system in adults. In approximately 50% of tumors with EGFR amplification, a specific EGFR mutant (EGFRvIII, also known as EGFR type III, de2-7,Delta EGFR) can be detected. This mutant is highly oncogenic and is generated from a deletion of exons 2 to 7 of the EGFR gene, which results in an in-frame deletion of 267 amino acids from the extracellular domain of the receptor. EGFRvIII is unable to bind ligand, and it signals constitutively. Although EGFRvIII has the same signaling domain as the wild type receptor, it seems to generate a distinct set of downstream signals that may contribute to an increased tumorigenicity. In this review, we discuss recent progress in key aspects of EGFR signaling in GBM, focusing on neuropathology, signal transduction, imaging of the EGFR, and the role of the EGFR in mediating resistance to radiation therapy in GBM.