Targeting erbB receptors.
Targeting erbB receptors.
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DOI：
10.1016/j.semcdb.2010.09.005
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发表时间：
2010-12
影响因子：
7.3
通讯作者：
Greene MI
中科院分区：
文献类型：
--
作者：
Cai Z;Zhang H;Liu J;Berezov A;Murali R;Wang Q;Greene MI
我们的工作涉及人类癌症的起源和治疗。酪氨酸激酶的表皮生长因子受体（EGFR）家族的成员，也称为erbB或HER受体，在许多类型的人类肿瘤中过表达和/或活化，并且代表癌症治疗中的重要治疗靶标。我们实验室的研究将靶向治疗确定为治疗癌症的一种方法。已经开发了靶向和禁用erbB受体的合理疗法来逆转肿瘤的恶性性质。使用单克隆抗体使HER 2受体失能时最好地观察到的恶性表型的恢复是与阻断配体与同源受体结合所观察到的过程不同的过程，如对EGFr受体所做的那样。在这里，我们回顾了从我们实验室和其他地方开发的一些方法推导出的作用机制，包括单克隆抗体，肽模拟物，重组蛋白和小分子。在这些使HER 2同聚体或HER 2-EGFr异聚体受体失能的研究中发现的生物化学和生物学原理将有助于开发靶向erbB家族受体的新型和更有效的治疗剂。
Our work is concerned with the origins and therapy of human cancers. Members of the epidermal growth factor receptor (EGFR) family of tyrosine kinases, also known as erbB or HER receptors, are over expressed and/or activated in many types of human tumors and represent important therapeutic targets in cancer therapy. Studies from our laboratory identified targeted therapy as a way to treat cancer. Rational therapeutics targeting and disabling erbB receptors have been developed to reverse the malignant properties of tumors. Reversal of the malignant phenotype, best seen with disabling the HER2 receptors using monoclonal antibodies is a distinct process from that seen with blocking of ligand binding to cognate receptors as has been done for EGFr receptors. Here we review the mechanisms of action deduced from a number of approaches developed in our laboratory and elsewhere, including monoclonal antibodies, peptide mimetics, recombinant proteins and small molecules. The biochemical and biological principles which have been uncovered during these studies of disabling HER2 homomeric or HER2-EGFr heteromeric receptors will help the development of novel and more efficient therapeutics targeting erbB family receptors.
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