Department of Systems Biology, The University of Texas MD Anderson Cancer Center Houston, TX, USA.
Front Oncol. 2012 Jun 18;2:62. doi: 10.3389/fonc.2012.00062. eCollection 2012.
HER2-positive breast cancer accounts for 20-30% of all breast cancers and has the second-poorest prognosis among breast cancer subtypes. The approval of trastuzumab in 1998 has significantly improved patients' outcomes and paved the way for the beginning of advent of targeted approaches in breast cancer treatment. However, primary or acquired resistance to trastuzumab has been increasingly recognized as a major obstacle in the clinical management of this disease. In addition, in clinical practice, there are currently no conclusive biomarkers for patient response to trastuzumab. Therefore, understanding the molecular mechanism of trastuzumab and the development of resistance to this drug are of interest. Such understanding will provide the guidance critically needed for the design of better combination therapy and will allow the appropriate selection of patients who are responsive to trastuzumab-based strategies. In line with that, our review highlights the well-accepted mechanisms of action and resistance to the therapy and discusses the progress that has been made toward successfully overcoming this resistance.
人表皮生长因子受体 2 阳性乳腺癌占所有乳腺癌的 20-30%，在乳腺癌亚型中预后最差。1998 年曲妥珠单抗的获批显著改善了患者的预后，并为乳腺癌治疗中靶向方法的出现奠定了基础。然而，曲妥珠单抗的原发性或获得性耐药已日益成为该疾病临床管理的主要障碍。此外，在临床实践中，目前尚无明确的生物标志物可预测患者对曲妥珠单抗的反应。因此，了解曲妥珠单抗的分子机制及其耐药性的发展具有重要意义。这种理解将为更好的联合治疗方案的设计提供至关重要的指导，并允许对响应曲妥珠单抗治疗策略的患者进行适当选择。为此，我们的综述强调了该疗法的公认作用机制和耐药机制，并讨论了在成功克服这种耐药性方面取得的进展。
