Oncogenic growth factor receptors: implications for signal transduction therapy
Oncogenic growth factor receptors: implications for signal transduction therapy
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DOI：
10.1016/j.semcancer.2004.04.005
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发表时间：
2004-08-01
影响因子：
14.5
通讯作者：
Yarden, Y
中科院分区：
文献类型：
--
作者：
Mosesson, Y;Yarden, Y
EGF 家族的生长因子及其各自的 ErbB/HER 受体酪氨酸激酶是肿瘤细胞许多标志性的基础，包括过度生长、侵袭行为和血管吸引。在人类癌症中经常观察到 ErbB 蛋白表达的增强、永久活性受体突变体的存在以及自分泌环的出现，并且在某些情况下它们与不良的疾病结果相关。四种 ErbB 蛋白及其 11 个配体在由最具致癌性的家族成员 ErbB-2/HER2 协调的分层信号网络内发挥作用。拦截 ErbB-2 和 ErbB-1 发出的信号的药物已在常规临床应用中。在这里，我们回顾了开发新的 ErbB 靶向疗法的三种主要策略。这些是单克隆抗受体抗体、特异性酪氨酸激酶抑制剂和热休克蛋白 90 拮抗剂。对其潜在机制进行了严格的研究，重点是潜在的药物组合，这些药物组合有望增强临床疗效。 (C) 2004 Elsevier Ltd. 保留所有权利。
Growth factors of the EGF family and their respective ErbB/HER receptor tyrosine kinases underlie many landmarks of tumor cells, including excessive growth, invasive behavior and attraction of blood vessels. Enhanced expression of ErbB proteins, existence of permanently active receptor mutants and occurrence of autocrine loops are frequently observed in human cancer, and in some cases they associate with poor disease outcome. The four ErbB proteins and their 11 ligands act within a layered signaling network coordinated by ErbB-2/HER2, the most oncogenic family member. Drugs that intercept signals emanating from ErbB-2 and ErbB-1 are already in routine clinical application. Here we review three major strategies to develop new ErbB-targeted therapies. These are monoclonal anti-receptor antibodies, specific tyrosine kinase inhibitors and antagonists of heat shock protein 90. The underlying mechanisms are critically examined, with an emphasis on potential drug combinations, which hold promise for enhanced clinical efficacy. (C) 2004 Elsevier Ltd. All rights reserved.