HER2 is an established therapeutic target in a large subset of women with breast cancer; a variety of agents including trastuzumab, pertuzumab, lapatinib, neratinib and trastuzumab emtansine (T-DM1) have been approved for the treatment of HER2-positive breast cancer. HER2 is also overexpressed in subsets of patients with other solid tumours. Notably, the addition of trastuzumab to first-line chemotherapy has improved the overall survival of patients with HER2-positive gastric cancer, and has become the standard-of-care treatment for this group of patients. However, trials involving pertuzumab, lapatinib and T-DM1 have failed to provide significant improvements in the outcomes of patients with HER2-positive gastric cancer. HER2-targeted therapies are also being tested in patients with other solid tumours harbouring HER2 overexpression, and/or amplifications or other mutations of the gene encoding HER2 (ERBB2), including biliary tract, colorectal, non-small-cell lung and bladder cancers. The experience with gastric cancer suggests that the successes observed in HER2-positive breast cancer might not be replicated in these other tumour types, owing to differences in the level of HER2 overexpression and other aspects of disease biology. In this Review, we describe the current role of HER2-targeted therapies beyond breast cancer and also highlight the potential of novel HER2-targeted agents that are currently in clinical development.

中文翻译：

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HER2靶向疗法——超越乳腺癌的作用。

HER2是大部分乳腺癌女性的既定治疗靶点；包括曲妥珠单抗、帕妥珠单抗、拉帕替尼、来那替尼和曲妥珠单抗 emtansine (T-DM1) 在内的多种药物已被批准用于治疗 HER2 阳性乳腺癌。HER2 在患有其他实体瘤的患者亚群中也过表达。值得注意的是，在一线化疗中加用曲妥珠单抗，提高了HER2阳性胃癌患者的总体生存率，成为该组患者的标准治疗方案。然而，涉及帕妥珠单抗、拉帕替尼和 T-DM1 的试验未能显着改善 HER2 阳性胃癌患者的预后。HER2靶向疗法也在其他携带HER2过表达的实体瘤患者中进行测试，和/或编码 HER2 (ERBB2) 的基因的扩增或其他突变，包括胆道癌、结直肠癌、非小细胞肺癌和膀胱癌。胃癌的经验表明，由于 HER2 过表达水平和疾病生物学的其他方面存在差异，在 HER2 阳性乳腺癌中观察到的成功可能无法在这些其他肿瘤类型中复制。在这篇综述中，我们描述了 HER2 靶向治疗在乳腺癌之外的当前作用，并强调了目前正在临床开发中的新型 HER2 靶向药物的潜力。胃癌的经验表明，由于 HER2 过表达水平和疾病生物学的其他方面存在差异，在 HER2 阳性乳腺癌中观察到的成功可能无法在这些其他肿瘤类型中复制。在这篇综述中，我们描述了 HER2 靶向治疗在乳腺癌之外的当前作用，并强调了目前正在临床开发中的新型 HER2 靶向药物的潜力。胃癌的经验表明，由于 HER2 过表达水平和疾病生物学的其他方面存在差异，在 HER2 阳性乳腺癌中观察到的成功可能无法在这些其他肿瘤类型中复制。在这篇综述中，我们描述了 HER2 靶向治疗在乳腺癌之外的当前作用，并强调了目前正在临床开发中的新型 HER2 靶向药物的潜力。