Selective inhibition of HER2 inhibits AKT signal transduction and prolongs disease-free survival in a micrometastasis model of ovarian carcinoma
Selective inhibition of HER2 inhibits AKT signal transduction and prolongs disease-free survival in a micrometastasis model of ovarian carcinoma
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DOI：
10.1093/annonc/mdi405
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发表时间：
2005-12-01
影响因子：
50.5
通讯作者：
Canal, P
中科院分区：
文献类型：
--
作者：
Delord, JP;Allal, C;Canal, P
虽然一线化疗在许多上皮性卵巢癌病例中诱导完全临床缓解，但由于微转移，复发通常发生在诊断后18-28个月。本研究旨在评估曲妥珠单抗对专门设计的卵巢癌小鼠模型（OVCAR-3）的无病生存期和总生存期的影响，该模型模拟了人类微转移性疾病的自然史。如果在诱导化疗后不久开始，曲妥珠单抗可以治愈小鼠。它通过丝裂原活化蛋白激酶信号转导适度抑制细胞增殖，并明显抑制参与生存通路的AKT磷酸化。由于OVCAR-3细胞系未显示HER 2扩增或过表达，因此这些结果需要进一步研究，以评估曲妥珠单抗在除过表达HER 2的癌症模型以外的癌症模型中复发早期的疗效。
Although first-line chemotherapy induces complete clinical remission in many cases of epithelial ovarian cancer, relapse usually occurs 18-28 months from diagnosis owing to micrometastases. The present study aimed to evaluate the effect of trastuzumab on disease-free and overall survival in a specially designed murine model of ovarian cancer (OVCAR-3), which mimicked the natural history of human micrometastatic disease. Trastuzumab can cure the mice if started soon after induction chemotherapy. It can modestly inhibit the proliferation through mitogen-activated protein kinase signal transduction and clearly inhibit AKT phosphorylation, which is involved in survival pathway. As OVCAR-3 cell lines show no HER2 amplification or overexpression, these results warrant further studies to assess the efficacy of trastuzumab in the early stage of relapse in cancer models other than those overexpressing HER2.