结直肠癌（CRC）代表着全球健康威胁，是全球癌症相关死亡的第二大原因。靶向治疗为转移期带来了新的希望，而转移期历来预后很差。约 5% 的转移性结直肠癌 (mCRC) 患者存在人表皮生长受体 2 (HER2) 过度表达，包括基因扩增和点突变。尽管其预后作用存在争议，但临床前和临床数据表明 HER2 作为抗 EGFR 治疗反应的阴性预测生物标志物。基于组织和血浆的 NGS 测试可以在基线和治疗期间精确识别这种耐药机制，从而指导决策。此外，已完成和正在进行的随机试验也取得了有希望的结果，将 HER2 作为可行的靶点进行测试。在这篇综述中，我们讨论了晚期 CRC 中 HER2 靶向的现有证据，分析了其在治疗算法中未来可能发挥的作用。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Colorectal cancer (CRC) represents a global health threat, standing as the second leading cause of cancer-related death worldwide. Targeted therapies brought new hope for the metastatic stage, which historically bore a very poor prognosis. Human epidermal growth receptor 2 (HER2) overexpression concerns about 5 % of the metastatic CRC (mCRC) patients, including both gene amplifications and point mutations. Albeit its controversial prognostic role, preclinical and clinical data indicate HER2 as a negative predictive biomarker of response to anti-EGFR therapies. Tissue and plasma-based NGS testing, could permit a precise identification of this resistance mechanism both at baseline and during treatment, thus guiding decision-making. Furthermore, promising results come from completed and ongoing randomized trials, testing HER2 as an actionable target. In this review, we discuss the available evidence on HER2 targeting in advanced CRC, analyzing its possible future role in the treatment algorithm.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.