Department of Radiation Biology, Finsencenter, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
BioDrugs. 2012 Apr 1;26(2):83-99. doi: 10.2165/11599760-000000000-00000.
The epidermal growth factor receptor (EGFR) is over-expressed, as well as mutated, in many types of cancers. In particular, the EGFR variant type III mutant (EGFRvIII) has attracted much attention as it is frequently and exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal agents to the EGFR/EGFRvIII-positive cells; among these are radio-labelled mAbs and immunotoxins. This article reviews the current status and efficacy of EGFR/EGFRvIII-targeted therapies.
表皮生长因子受体（EGFR）在许多类型的癌症中过度表达和突变。特别是，EGFR 变体 III 型突变体（EGFRvIII）引起了广泛关注，因为它经常且仅在许多肿瘤细胞上发现，因此 EGFR 和 EGFRvIII 都被提出作为许多癌症治疗方案中的有效靶点。已经开发了不同的策略来抑制 EGFR/EGFRvIII 的活性或消除 EGFR/EGFRvIII 阳性肿瘤细胞。抑制这些受体的药物包括与 EGFR 的细胞外部分结合的单克隆抗体（mAbs），阻断 EGFR 配体的结合位点，以及抑制酪氨酸激酶结构域的 ATP 结合位点的细胞内酪氨酸激酶抑制剂（TKIs）。除了针对 EGFRvIII 的疫苗外，在不同的情况下还使用了偶联的抗 EGFR mAbs 将致命剂递送到 EGFR/EGFRvIII 阳性细胞；其中包括放射性标记的 mAbs 和免疫毒素。本文综述了针对 EGFR/EGFRvIII 的靶向治疗的现状和疗效。
