Human epidermal growth factor receptor-2 (HER2) is a well-known cancer target. Many HER2-targeted agents are marketed and being investigated. Unfortunately, these therapies lack consistent responses and outcomes amongst different tumors. Questions remain as to why HER2 biology is different in different tumor types. Gastric adenocarcinomas (GACs) demonstrate both intra- and inter-tumor HER2 expression heterogeneity and show discordance amongst primary and metastatic disease sites. This creates barriers in determining HER2 agents’ effectiveness and contributes to the failure of some HER2-targeted agents in the treatment of HER2-positive advanced GACs. Trastuzumab deruxtecan, an antibody drug conjugate of trastuzumab with a topoisomerase inhibitor, was recently approved for the treatment of refractory HER2-positive advanced GAC patients. There are exciting and newer therapies under investigation. Examining resistance patterns (both adaptive and acquired) along with establishing a better understanding of the intra- and inter-tumor heterogeneity is necessary to ensure successful progress. Here we review the current status of HER2-targeted therapy in GACs. We additionally review newer therapies under investigation and their potential role in HER2 GACs.
人表皮生长因子受体2（HER2）是公认的癌症治疗靶点。目前已有多种HER2靶向药物上市并处于研究阶段。然而，这些疗法在不同肿瘤类型中缺乏一致的治疗反应和临床结局。关于HER2生物学特性在不同肿瘤类型中存在差异的原因仍有待阐明。胃腺癌（GACs）表现出显著的瘤内及瘤间HER2表达异质性，且原发灶与转移灶之间存在表达不一致现象。这种异质性为评估HER2靶向药物疗效带来挑战，也是部分HER2靶向药物治疗HER2阳性晚期胃腺癌失败的重要原因。新型抗体偶联药物德曲妥珠单抗（由曲妥珠单抗与拓扑异构酶抑制剂偶联而成）近期获批用于难治性HER2阳性晚期胃腺癌的治疗。目前尚有诸多创新疗法处于研究阶段。为推进治疗进展，必须系统研究耐药机制（包括适应性耐药与获得性耐药），并深入理解肿瘤内及肿瘤间的异质性特征。本文综述了当前HER2靶向治疗在胃腺癌领域的应用现状，同时探讨了正在研发的新型疗法及其在HER2阳性胃腺癌治疗中的潜在价值。
肿瘤(癌症)患者之家