The receptor tyrosine-kinase HER2 (also known as ErbB2) is a well-established therapeutic target in patients with breast or gastric cancer selected on the basis of HER2 overexpression on immunohistochemistry and/or ERBB2 amplification on in situ hybridization. With advances in cancer molecular profiling and increased implementation of precision medicine approaches into oncology practice, actionable HER2 alterations in solid tumours have expanded to include ERBB2 mutations in addition to traditional HER2 overexpression and ERBB2 amplification. These various HER2 alterations can be found in solid tumour types beyond breast and gastric cancer, although few HER2-targeted therapeutic options have been established for the other tumour types. Nevertheless, during the 5 years since our previous Review on this topic was published in this journal, obvious and fruitful progress in the development of HER2-targeted therapies has been made, including new disease indications, innovative drugs with diverse mechanisms of action and novel frameworks for approval by regulatory authorities. These advances have culminated in the recent histology-agnostic approval of the anti-HER2 antibody–drug conjugate trastuzumab deruxtecan for patients with HER2-overexpressing solid tumours. In this new Review, we provide an update on the current development landscape of HER2-targeted therapies beyond breast cancer, as well as anticipated future HER2-directed treatment strategies to overcome resistance and thereby improve efficacy and patient outcomes.

受体酪氨酸激酶 HER2（也称为 ErbB2）是乳腺癌或胃癌患者的公认治疗靶点，根据免疫组织化学上 HER2 过表达和/或 ERBB2 原位杂交扩增来选择。随着癌症分子分析的进步和精准医学方法在肿瘤学实践中的更多实施，实体瘤中可操作的 HER2 改变已经扩展到除了传统的 HER2 过表达和 ERBB2 扩增外，还包括 ERBB2 突变。这些不同的 HER2 改变可以在乳腺癌和胃癌以外的实体瘤类型中找到，尽管很少有针对其他肿瘤类型的 HER2 靶向治疗方案。尽管如此，自我们之前关于该主题的综述在本杂志上发表以来的 5 年里，HER2 靶向疗法的开发已经取得了明显而富有成效的进展，包括新的疾病适应症、具有不同作用机制的创新药物和监管机构批准的新框架。这些进展最终导致最近抗 HER2 抗体-药物偶联物曲妥珠单抗 deruxtecan 的组织学不可知批准用于 HER2 过表达实体瘤患者。在这篇新综述中，我们提供了乳腺癌以外 HER2 靶向治疗的当前发展前景的最新信息，以及预期的未来 HER2 靶向治疗策略，以克服耐药性，从而提高疗效和患者预后。