The role of c-erbB-2/HER2/neu in breast cancer progression and metastasis
The role of c-erbB-2/HER2/neu in breast cancer progression and metastasis
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DOI：
10.1023/a:1014730829872
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发表时间：
2001-10-01
影响因子：
2.5
通讯作者：
Eceles, SA
中科院分区：
文献类型：
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作者：
Eceles, SA
c-erbB-2/HER2/新酪氨酸激酶基因扩增和/或过表达与乳腺癌预后不良有关。这表现为无病期缩短，转移风险增加。以及对多种疗法的抵抗。这些现象背后的分子机制和信号通路现在正在被阐明。c-erbB-2虽然没有已知的可溶性配体，但可以通过与其他家族成员的异源二聚化（EGFR）进行反激活。c-erbB-3。c-erbB-4)。受体激活增强肿瘤细胞运动、蛋白酶分泌和侵袭，也调节细胞周期检查点功能、DNA修复和凋亡反应。由于c-erbB-2在正常成人组织中表达水平较低，因此它是治疗的理想靶点。我们有理由乐观地认为，靶向c-erbB-2信号的药物将对乳腺癌产生深远的选择性作用，无论是作为单一药物，还是更有可能与其他治疗药物联合使用，以增强其效力。
Gene amplification and/or overexpression of the c-erbB-2/HER2/neu tyrosine kinase are linked with poor prognosis in breast cancer. This is manifest in shorter disease-free intervals, increased risk of metastasis. and resistance to many types of therapy. The molecular mechanisms and signaling circuitry underlying these phenomena are now being elucidated. c-erbB-2, although having no known soluble ligand, is transactivated by heterodimerization with other family members (EGFR. c-erbB-3. c-erbB-4). Receptor activation potentiates tumor cell motility, protease secretion and invasion, and also modulates cell cycle checkpoint function, DNA repair, and apoptotic responses. Since it is expressed at low levels in normal adult tissues, c-erbB-2 is an ideal target for therapy. There is reason for optimism that agents targeting c-erbB-2 signaling will have profound and selective effects in breast cancer, either as single agents or more likely in combination with other therapeutic agents, to enhance their potency.