Despite a decreasing incidence in Western countries, gastric cancer is among the most common cancer subtypes globally and is associated with one of the highest tumor-related mortality rates. Biomarkers play an increasing role in the treatment against gastric cancer. HER2 was one of the first biomarkers that found its way into clinical practice. Since the ToGA trial, trastuzumab has been part of first-line palliative chemotherapy in metastatic or unresectable gastric cancer. HER2-targeting agents, such as the tyrosine kinase inhibitor lapatinib, the antibody drug conjugate (ADC) trastuzumab-emtansine or dual HER2 inhibition (pertuzumab and trastuzumab), have been investigated in the second-line setting but led to negative study results. More recently, the ADC trastuzumab-deruxtecan was authorized after the failure of trastuzumab-based treatment. However, further improvements in HER2-directed therapy are required as resistance mechanisms and HER2 heterogeneity limit the existing treatment options. This review aims to give an overview of the current standard-of-care HER2-directed therapy in gastric cancer, as well as its challenges and future developments.
尽管在西方国家发病率有所下降，胃癌仍是全球最常见的癌症亚型之一，且肿瘤相关死亡率位居前列。生物标志物在胃癌治疗中的作用日益凸显。HER2是最早应用于临床实践的生物标志物之一。自ToGA试验以来，曲妥珠单抗已成为转移性或不可切除胃癌一线姑息化疗的组成部分。针对HER2的靶向药物，如酪氨酸激酶抑制剂拉帕替尼、抗体药物偶联物（ADC）曲妥珠单抗-美坦新衍生物或双重HER2抑制剂（帕妥珠单抗与曲妥珠单抗联合疗法），已在二线治疗中进行研究，但均未取得阳性试验结果。近期，基于曲妥珠单抗治疗失败后，ADC药物曲妥珠单抗-deruxtecan已获批准使用。然而，由于耐药机制和HER2异质性限制了现有治疗方案，HER2靶向治疗仍需进一步改进。本综述旨在概述当前胃癌HER2靶向治疗的标准方案、面临的挑战及未来发展方向。
HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments
肿瘤(癌症)患者之家