The ErbB receptors as targets for breast cancer therapy

The ErbB receptors as targets for breast cancer therapy
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DOI:
10.1023/a:1018762216147
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发表时间:
1999-10-01
影响因子:
2.5
通讯作者:
Baselga, J
Baselga, J
中科院分区:
医学4区
文献类型:
--
作者:
Albanell, J;Baselga, J

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乳腺癌表达高水平的 ErbB 受体及其配体,并且它们的过度表达与更具侵袭性的临床行为相关,因此针对这些受体的治疗有可能成为有用的抗癌治疗。目前正在评估一系列针对 EGF (ErbB1) 受体和密切相关的 HER2/Neu (ErbB2) 受体的单克隆抗体 (MAb)(3)。这些单克隆抗体已显示出有希望的临床前活性,并且已生产出“嵌合”和“人源化”单克隆抗体,以避免宿主免疫反应的问题。这些抗体目前正在临床试验中单独或与化疗药物联合进行测试。其中一种抗体曲妥珠单抗(一种人源化抗 ErbB2 MAb)的临床活性已在一系列临床试验中在乳腺癌患者中得到记录,并且最近被批准用于治疗转移性 ErbB2 过表达乳腺癌患者。除了抗体之外,抑制受体酪氨酸激酶的化合物也显示出显着的临床前活性,目前正在临床中进行评估。
Breast carcinomas express high levels of ErbB receptors and their ligands, and their overexpression has been associated with a more aggressive clinical behavior For these reasons therapies directed at these receptors have the potential to be useful anti-cancer treatments. A series of monoclonal antibodies (MAbs)(3) directed against the EGF (ErbB1) receptor and the closely related HER2/Neu (ErbB2) receptor are currently under evaluation. These MAbs have shown promising preclinical activity and "chimeric" and "humanized" MAbs have been produced in order to obviate the problem of host immune reactions. These antibodies are currently bring tested in clinical trials either alone or in combination with chemotherapeutic agents. Clinical activity with one of these antibodies, trastuzumab, a humanized anti-ErbB2 MAb, has been documented in patients with breast cancer in a series of clinical trials and has recently been approved for the therapy of patients with metastatic ErbB2 overexpressing breast cancer. In addition to antibodies, compounds that inhibit receptor tyrosine kinases have shown significant preclinical activity and are currently bring evaluated in the clinic.