Gastric cancer (GC) is one of the most heterogeneous and aggressive malignant tumors of the digestive system. Traditional chemotherapy drugs and epidermal growth factor receptor 2 (HER2) targeted drugs such as Trastuzumab still have the disadvantages of high incidence of drug resistance, high toxic side effects and poor tolerance of patients. Therefore, it is imperative to develop more effective anti GC drugs. Novel targeted drugs against HER2 are currently available, but are ineffective or resistance in some cases, which is related to the low expression of HER2 (HER2 IHC1+ or IHC2+/ISH-) in certain GC cells, accounting for about 40%-60% of all types. However, in clinical practice, these patients are still reported as HER2-negative GC. Therefore, accurate detection of HER2 expression is crucial to identify patients who may benefit from trastuzumab therapy. The emergence of antibody drug conjugates (ADC) provides a new therapeutic option for HER2-positive GC and it is expected to replace traditional GC chemotherapy in the future by its precise and efficient anti-tumor effect. Recent studies have found that ADC may have potential anti-tumor activity in HER2 low-expression GC, and related clinical studies are evaluating its effectiveness and safety in HER2 low-expression GC treatment. This article reviews the application and the latest research progress of ADC in HER2 low-expression GC patients in the era of targeted therapy and discusses the challenges faced in the application and development of HER2-targeted ADCs.

胃癌（GC）是极具异质性和侵袭性的消化系统恶性肿瘤之一，传统化疗药物及曲妥珠单抗等人表皮生长因子受体2（HER2）靶向药物在GC的治疗过程中仍然存在耐药性发生率高、毒副作用大、患者耐受差等缺点。因此，研发更为有效的抗GC药物势在必行。目前针对HER2的新型靶向药层出不穷，但在某些情况下无效或产生耐药，这与HER2在某些GC细胞中低表达有关，HER2低表达（HER2 IHC1+或IHC2+/ISH-）约占全部类型的40%~60%，但在临床实践中，这类患者仍被报告为HER2阴性GC。因此准确检测HER2表达状态对于确定可能受益于曲妥珠单抗治疗的患者至关重要。抗体药物偶联物（ADC）的出现为HER2阳性GC提供了新的治疗选择，凭借其精准高效的抗肿瘤作用，有望在未来替代传统GC化学疗法。近期有研究发现ADC可能在HER2低表达GC中具有潜在抗肿瘤活性，相关临床研究正在评估其在HER2低表达GC治疗中的有效性和安全性。本文就靶向治疗时代ADC在HER2低表达GC患者中的应用和最新研究进展作一综述，并讨论HER2靶向ADC在应用和研发过程中面临的挑战。