Cardoso Fatima, Piccart Martine J, Durbecq Virginie, Di Leo Angelo
Chemotherapy and Translational Research Units, Jules Bordet Institute, Boulevard de Waterloo, 125 1000 Brussels, Belgium.
Clin Breast Cancer. 2002 Oct;3(4):247-57; discussion 258-9. doi: 10.3816/CBC.2002.n.028.
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.
这篇综述文章的目的是研究对曲妥珠单抗耐药的潜在机制。在临床环境中，当曲妥珠单抗作为单一药物用于一线治疗HER2过表达的转移性乳腺癌时，其客观缓解率为40%。在其余病例中，尽管HER2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HER2外的其他一些因素必定在决定对曲妥珠单抗的敏感程度中发挥作用。确定对曲妥珠单抗耐药的潜在机制对于开发新化合物非常有帮助，这些新化合物可能克服耐药性和/或与曲妥珠单抗联合使用时具有相加/协同抗肿瘤作用。此外，深入了解HER2通路对于确定曲妥珠单抗反应的新预测标志物至关重要，这将有助于更好地界定最可能从该药物中获益的患者。
