Since several years targeted therapy has been part of treatment in NSCLC in subsets of patients with specific genetic alterations. One of these alterations involves HER2, a member of the ERBB family of tyrosine kinase receptors. Despite that HER2 alterations in NSCLC have been studied for years, there is still no consensus about subgroup definitions. In this review HER2 alterations in NSCLC are discussed, including diagnostic challenges and treatment strategies. Three principal mechanisms of HER2 alterations can be identified: HER2 protein overexpression, HER2 gene amplification and HER2 gene mutations. There are several methods for the detection of HER2 "positivity" in NSCLC, but no gold standard has been established. Laboratory methods for assessment of HER2 positivity in NSCLC include immunohistochemistry (IHC) for protein overexpression and fluorescent in situ hybridization (FISH) and next generation sequencing (NGS) for genetic alterations. Many trials testing HER2 targeted therapy in HER2 altered NSCLC has not lead to a renewed standard of care for this group of patients. Therefore, today the (re)search on how to analyse, define and treat HER2 alterations in NSCLC continues. Still there is no consensus about HER2 subgroup definitions and results of the many trials studying possible treatment strategies are inconclusive. Future research should focus on the most important missing link, whether all HER2 alterations are relevant oncogenic drivers and whether it should be considered as a therapeutic target in NSCLC.

中文翻译：

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HER2的作用力-NSCLC的可治疗靶标？

自几年以来，靶向治疗已成为具有特定基因改变的患者亚组NSCLC治疗的一部分。这些变化之一涉及HER2，它是酪氨酸激酶受体ERBB家族的成员。尽管已经研究了NSCLC中的HER2改变，但对于亚组的定义仍未达成共识。在这篇综述中，讨论了NSCLC中的HER2改变，包括诊断挑战和治疗策略。可以确定HER2改变的三种主要机理：HER2蛋白的过表达，HER2基因的扩增和HER2基因的突变。在NSCLC中有几种检测HER2“阳性”的方法，但尚未建立金标准。评估NSCLC中HER2阳性的实验室方法包括用于蛋白质过表达的免疫组织化学（IHC）和用于基因改变的荧光原位杂交（FISH）和下一代测序（NGS）。许多在HER2改变的NSCLC中测试HER2靶向疗法的试验并未导致该组患者的新护理标准。因此，今天，关于如何分析，定义和治疗NSCLC中HER2改变的（重新）研究仍在继续。关于HER2亚组的定义仍未达成共识，许多研究可能的治疗策略的试验结果尚无定论。未来的研究应集中在最重要的缺失环节上，即所有HER2改变是否均与致癌因素有关，以及是否应将其视为NSCLC的治疗靶标。