Biological and clinical significance of HER2 overexpression in breast cancer.
Biological and clinical significance of HER2 overexpression in breast cancer.
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DOI：
10.1007/bf02967477
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发表时间：
2001-01-01
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影响因子：
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通讯作者：
Kurebayashi , J
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作者：
Kurebayashi , J
HER-2/neu原癌基因的产物HER 2是酪氨酸激酶受体的人表皮生长因子受体（HER）家族的第二个成员，并且已被认为是配体孤儿受体。HER 2和另一个HER家族成员HER 1、HER 3或HER 4之间的配体依赖性异二聚化激活HER 2信号传导途径。HER 2的细胞内信号传导途径被认为涉及ras-MAPK、MAPK非依赖性S6激酶和磷脂酶C-γ信号传导途径。然而，这些途径激活的生物学后果尚未完全清楚。HER 2基因的扩增和HER 2蛋白的过表达诱导细胞转化，并且已在10%至40%的人乳腺癌中得到证实。HER 2过表达与乳腺癌患者的肿瘤侵袭性、预后以及对激素和细胞毒性药物的反应性有关。这些发现表明，HER 2是肿瘤特异性治疗的合适靶点。已经研究了许多方法：（1）针对HER 2的人源化单克隆抗体，rhuMAbHER 2（曲妥珠单抗），其已被批准用于治疗转移性乳腺癌患者的临床用途;（2）酪氨酸激酶抑制剂，如大黄素，其阻断HER 2磷酸化及其细胞内信号传导;（3）主动免疫疗法，如疫苗接种;和（4）热休克蛋白（Hsp）90相关信号抑制剂，如根赤霉素衍生物，其诱导酪氨酸激酶受体如HER 2的降解。
The product of the HER-2/neu proto-oncogene, HER2, is the second member of the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors and has been suggested to be a ligand orphan receptor. Ligand-dependent heterodimerization between HER2 and another HER family member, HER1, HER3 or HER4, activates the HER2 signaling pathway. The intracellular signaling pathway of HER2 is thought to involve ras-MAPK, MAPK-independent S6 kinase and phospholipase C-gamma signaling pathways. However, the biological consequences of the activation of these pathways are not yet completely known. Amplification of the HER2 gene and overexpression of the HER2 protein induces cell transformation and has been demonstrated in 10% to 40% of human breast cancer. HER2 overexpression has been suggested to associate with tumor aggressiveness, prognosis and responsiveness to hormonal and cytotoxic agents in breast cancer patients. These findings indicate that HER2 is an appropriate target for tumor-specific therapies. A number of approaches have been investigated: (1) a humanized monoclonal antibody against HER2, rhuMAbHER2 (trastuzumab), which is already approved for clinical use in the treatment of patients with metastatic breast cancer; (2) tyrosine kinase inhibitors, such as emodin, which block HER2 phosphorylation and its intracellullar signaling; (3) active immunotherapy, such as vaccination; and (4) heat shock protein (Hsp) 90-associated signal inhibitors, such as radicicol derivatives, which induce degradation of tyrosine kinase receptors, such as HER2.