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Abstract：
The development of trastuzumab is among the most significant cancer drug development projects in the 20th century. Trastuzumab became a gamechanger for the treatment of human epidermal growth receptor 2 (HER2) positive breast cancer, with a significant positive impact on disease recurrence and survival. The development of trastuzumab was the beginning of a new era of cancer drug development, which showed us the importance of understanding the molecular pathophysiology and drug mechanism of action. The drug-diagnostic codevelopment model, in which the drug is developed in parallel with a predictive biomarker assay, has had a significant impact on today\'s cancer drug development, and we are indebted to trastuzumab when it comes to the clinical enrichment trial design. Trastuzumab is not the only drug developed to target the HER2 protein. Over the past few decades, several new HER2 targeted therapies have been developed, including small-molecule tyrosine kinase inhibitors (TKI), monoclonal antibodies, and antibody-drug conjugates (ADC). In particular, the ADC trastuzumab deruxtecan seems to pave new avenues when it comes to HER2 targeted treatment not only for breast cancer, but also for gastric cancer and non-small cell lung cancer. With the development of trastuzumab as a reference point, this article will provide a brief summary of the efficacy of HER2 targeted therapy, including testing for HER2 positivity, as it has evolved over the past 25 years.
摘要：
曲妥珠单抗的开发是20世纪最重要的癌症药物开发项目之一。曲妥珠单抗成为治疗人类表皮生长受体2（HER2）阳性乳腺癌的游戏者，对疾病复发和生存率有显著的积极影响。曲妥珠单抗的开发是癌症药物开发新时代的开始，这表明了我们了解分子病理生理学和药物作用机制的重要性。药物-诊断共同发展模式，其中该药物与预测性生物标志物测定平行开发，对今天的癌症药物开发产生了重大影响，当涉及到临床富集试验设计时,我们感谢曲妥珠单抗.曲妥珠单抗并不是唯一针对HER2蛋白开发的药物。在过去的几十年里，已经开发了几种新的HER2靶向疗法，包括小分子酪氨酸激酶抑制剂（TKI），单克隆抗体，和抗体-药物缀合物(ADC)。特别是,ADC曲妥珠单抗deruxtecan似乎为HER2靶向治疗提供了新的途径，不仅针对乳腺癌，也适用于胃癌和非小细胞肺癌。随着曲妥珠单抗作为参考点的发展，本文将对HER2靶向治疗的疗效进行简要总结,包括HER2阳性测试，因为它在过去25年中不断发展。
