Baselga J, Albanell J, Molina M A, Arribas J
Medical Oncology Service, Vall D'Hebron University Hospital, Barcelona, Spain.
Semin Oncol. 2001 Oct;28(5 Suppl 16):4-11. doi: 10.1016/s0093-7754(01)90276-3.
The humanized anti-p185(HER2) monoclonal antibody trastuzumab has been shown to effectively inhibit the growth of HER2-overexpressing breast cancer cells in vivo and in vitro. The treatment of cancer cells with trastuzumab results in downregulation of the HER2 receptor. Further downstream cellular events include the accumulation of the cyclin-dependent kinase inhibitor p27 and cell cycle arrest. In vivo, trastuzumab induces antibody-dependent cellular cytotoxicity. Trastuzumab also inhibits constitutive HER2 cleavage/shedding mediated by metalloproteases. The ability of trastuzumab to inhibit HER2 cleavage may correlate with the clinical anticancer activity of the multifunctional HER2-targeting antibody.
人源化抗p185（HER2）单克隆抗体曲妥珠单抗已被证明在体内和体外均可有效抑制HER2过表达的乳腺癌细胞的生长。用曲妥珠单抗处理癌细胞会导致HER2受体下调。进一步的下游细胞事件包括细胞周期蛋白依赖性激酶抑制剂p27的积累和细胞周期停滞。在体内，曲妥珠单抗可诱导抗体依赖性细胞毒性。曲妥珠单抗还可抑制金属蛋白酶介导的组成型HER2裂解/脱落。曲妥珠单抗抑制HER2裂解的能力可能与其作为多功能HER2靶向抗体的临床抗癌活性相关。
