Abstract：
Among the molecular subgroups of interest in metastatic colorectal cancer (mCRC), innovations are underway for tumors with overexpression of HER2 (Human Epidermal Growth Factor Receptor 2). Overexpression of the HER2 protein concerns 2 to 5% of CRC at any stage mainly located in the distal colon and rectum. Diagnosis is based on immunohistochemistry, in situ hybridization with appropriate criteria for colorectal localization, and molecular biology (NGS: next-generation sequencing). Overexpression of HER2 is a predictive factor for resistance to treatments targeting EGFR which are indicated in the case where the tumor is wild-type RAS. It seems to be associated with a poor prognosis of mCRC with a higher risk of brain metastasis. Regarding treatments targeting HER2, no randomized controlled phase III has been published to date. However, several combinations have been evaluated in phase II with clinically meaningful objective response rates: trastuzumab-deruxtecan (45%), trastuzumab-tucatinib (46%), trastuzumab-pyrotinib (45%), trastuzumab-pertuzumab (30%) ou trastuzumab-lapatinib (30%). In this literature review, we present here the current state of knowledge on the diagnostic methods of HER2 overexpression in CRC, the main clinical, molecular and prognostic characteristics, and the efficacy results of the different therapeutic combinations for the patients with HER2 overexpressed mCRC. This justifies, despite the lack of marketing authorization in France and in Europe for agents targeting HER2 in CRC, the systematic evaluation of the HER2 status, as recommended in particular by the NCCN (National Comprehensive Cancer Network).
摘要：
在转移性结直肠癌（mCRC）感兴趣的分子亚组中，HER2(人类表皮生长因子受体2)过度表达的肿瘤正在进行创新.HER2蛋白的过表达涉及主要位于远端结肠和直肠的任何阶段的2-5%的CRC。诊断基于免疫组织化学，具有适当的结肠直肠定位标准的原位杂交，和分子生物学（NGS：下一代测序）。HER2的过表达是对靶向EGFR的治疗的抗性的预测因素,这在肿瘤是野生型RAS的情况下表明。它似乎与mCRC的不良预后有关，具有较高的脑转移风险。关于针对HER2的治疗，迄今为止尚未发表随机对照III期。然而,已在II期评估了几种组合，具有临床意义的客观缓解率：曲妥珠单抗-deruxtecan（45％），曲妥珠单抗-图卡替尼（46%），曲妥珠单抗-吡唑替尼（45%），曲妥珠单抗-帕妥珠单抗（30%）和曲妥珠单抗-拉帕替尼（30%）。在这篇文献综述中，我们在此介绍关于CRC中HER2过表达的诊断方法的现有知识，主要临床,分子和预后特征，以及不同治疗组合对HER2过表达mCRC患者的疗效结果。这证明了,尽管在法国和欧洲缺乏针对CRC中HER2的药物的营销授权，对HER2状态的系统评估，特别是NCCN（国家综合癌症网络）的建议。
