继表达 HER2 的乳腺癌治疗取得巨大成功后，针对表达人表皮生长因子受体 2 (HER2) 的胃癌的治疗进展也随之取得进展，这促进了抗 HER2 药物适应症的扩展，不仅包括传统的 HER2 - 阳性乳腺癌，还有 HER2 低和 HER2 超低亚组。然而，HER2 低胃癌的靶向性尚未确定。因此，需要进一步的研究来全面了解HER2低胃癌的临床病理特征、特异性基因改变和独特的肿瘤免疫微环境，并与HER2阳性或阴性胃癌进行比较。 HER2 抗体药物偶联物在靶向治疗 HER2 低的胃癌方面发挥着重要作用。在这种情况下，还需要更深入地了解新型抗 HER2 药物，包括抗体-药物缀合物、双特异性 T 细胞接合抗体以及这些药物的组合，以及新形式的免疫调节剂。不仅通过免疫组织化学/荧光原位杂交，而且通过评估 ERRB2 拷贝数增益或使用 DNA 或 RNA 测序测量的蛋白质过表达水平来重新定义和重新分类 HER2 状态，可能有助于识别患有 HER2 表达肿瘤的人群，这些人群理想地受益于抗-HER2治疗。本文回顾了最近的临床试验，特别关注 HER2 低胃癌以及基本/转化研究结果，并讨论了治疗这一独特亚组的进一步治疗发展的观点。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Therapeutic developments in the targeting of human epidermal growth factor receptor 2 (HER2)-expressing gastric cancer have followed the dramatic success of HER2-expressing breast cancer treatment, which has facilitated the expansion of indications for anti-HER2 agents to include not only conventional HER2-positive breast cancer, but also HER2-low and HER2-ultralow subgroups. The targetability of HER2-low gastric cancer, however, has yet to be established. Hence, further studies are needed to comprehensively understand the clinicopathological features, specific gene alterations, and distinct tumor immune microenvironment of HER2-low gastric cancer and compare them with those for HER2-positive or -negative gastric cancer. Antibody-drug conjugates for HER2 play an important role in making HER2-low gastric cancer targetable. In this context, a deeper understanding of the novel anti-HER2 agents, including antibody-drug conjugates, bispecific T-cell engager antibodies, and a combination of these agents, as well as new forms of immunomodulatory agents are also required. Redefining and re-categorizing HER2 status through not only immunohistochemistry/fluorescence in situ hybridization but also evaluating ERRB2 copy number gain or protein overexpression levels measured using DNA or RNA sequencing might be helpful for identifying populations with HER2-expressing tumors who would ideally benefit from anti-HER2 treatment. The current paper reviewed recent clinical trials, focusing particularly on HER2-low gastric cancer together with basic/translational findings, and discuss perspectives on further therapeutic development in the treatment of this distinct subgroup.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.