Resistance to trastuzumab: a necessary evil or a temporary challenge?
Resistance to trastuzumab: a necessary evil or a temporary challenge?
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DOI：
10.3816/cbc.2002.n.028
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发表时间：
2002-10-01
影响因子：
3.1
通讯作者：
Di Leo, Angelo
中科院分区：
文献类型：
--
作者：
Cardoso, Fatima;Piccart, Martine J;Di Leo, Angelo
这篇综述文章的目的是研究曲妥珠单抗耐药的潜在机制。在临床环境中，当曲妥珠单抗作为HER 2过表达转移性乳腺癌的一线治疗单药时，其客观缓解率为40%。在其余病例中，尽管HER 2蛋白过表达和/或相应基因扩增，但未观察到肿瘤消退。因此，除HER 2外的其他一些因素必须在确定对曲妥珠单抗的敏感性水平方面发挥作用。对曲妥珠单抗耐药的潜在机制的鉴定对于开发新化合物非常有帮助，当与曲妥珠单抗联合给药时，这些新化合物可能克服该耐药和/或具有相加/协同抗肿瘤作用。此外，彻底了解HER 2通路对于鉴定曲妥珠单抗反应的新预测标志物至关重要，这将有助于更好地确定最有可能从该药物中获益的患者。
The aim of this review article is to examine the potential mechanisms of resistance to trastuzumab. In the clinical setting, when trastuzumab is given as a single agent for first-line treatment of HER2-overexpressing metastatic breast cancer, it is associated with a 40% objective response rate. In the remaining cases, no tumor regression is observed, although HER2 protein is overexpressed and/or the corresponding gene is amplified. Hence, some other factors besides HER2 must play a role in determining the level of sensitivity to trastuzumab. The identification of the potential mechanisms of resistance to trastuzumab can be very helpful for the development of new compounds, which might overcome that resistance and/or have additive/synergistic antitumor effect when given in association with trastuzumab. Moreover, thorough understanding of the HER2 pathway is essential to the identification of new predictive markers of response to trastuzumab that will help to better define the patients who are most likely to benefit from this drug.