ErbB receptors and signaling pathways in cancer
ErbB receptors and signaling pathways in cancer
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DOI：
10.1016/j.ceb.2008.12.010
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发表时间：
2009-04-01
影响因子：
7.5
通讯作者：
MacDonald, Gwen
中科院分区：
文献类型：
--
作者：
Hynes, Nancy E.;MacDonald, Gwen
ErbB受体酪氨酸激酶在正常生理和癌症中发挥重要作用。表皮生长因子受体(EGFR)和ErbB2在许多上皮性肿瘤中都有突变，临床研究表明它们在肿瘤的发生发展中起着重要作用。人们对这些受体进行了深入的研究，不仅是为了了解它们潜在的致癌机制，也是为了将它们作为治疗的靶点。ErbB受体通过与多种信号转导分子相互作用激活多种细胞内通路。此外，现在有许多ErbB靶向抑制剂在临床上使用。在这篇综述中，我们将集中在ERBB2基因扩增/受体过表达的乳腺肿瘤和激活EGFR突变的非小细胞肺癌(NSCLC)。我们将讨论显示PI3K/Akt通路的重要作用的数据，不仅在癌症发展中，而且在靶向治疗中也是如此。最后，还将讨论导致ErbB靶向治疗耐药的机制。
The ErbB receptor tyrosine kinases play important roles in normal physiology and in cancer. Epidermal growth factor receptor (EGFR) and ErbB2 in particular are mutated in many epithelial tumors, and clinical studies suggest that they play roles in cancer development and progression. These receptors have been intensely studied, not only to understand the mechanisms underlying their oncogenic potential, but also to exploit them as therapeutic targets. ErbB receptors activate a multiplicity of intracellular pathways via their ability to interact with numerous signal transducers. Furthermore, there are now many ErbB-targeted inhibitors used in the clinic. In this review we will concentrate on breast tumors with ERBB2 gene amplification/receptor overexpression and non-small cell lung cancer (NSCLC) with activating EGFR mutations. We will discuss data showing the important role that the PI3K/Akt pathway plays, not only in cancer development, but also in response to targeted therapies. Finally, mechanisms contributing to resistance to ErbB-targeted therapeutics will also be discussed.