超越乳腺癌的 HER2 靶向疗法--最新进展

IF 81.1 1区 医学 Q1 ONCOLOGY
Jeesun Yoon, Do-Youn Oh
{"title":"超越乳腺癌的 HER2 靶向疗法--最新进展","authors":"Jeesun Yoon, Do-Youn Oh","doi":"10.1038/s41571-024-00924-9","DOIUrl":null,"url":null,"abstract":"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. Anti-HER2 therapy has revolutionized the treatment of HER2-positive breast cancer. However, HER2 has emerged as a driver of various other cancers and the indications for HER2-targeted therapy have expanded to include diverse HER2-overexpressing as well as HER2-mutant tumour types beyond breast cancer, facilitated by the advent of novel agents with greater potency and distinct mechanisms of action. Some of these agents have demonstrated promising activity even against HER2-low cancers. Herein, Yoon and Oh describe the landscape of HER2 alterations and HER2-targeted drug development beyond breast cancer. They also discuss new insights into mechanisms of resistance and potential strategies by which they might be overcome.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 9","pages":"675-700"},"PeriodicalIF":81.1000,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HER2-targeted therapies beyond breast cancer — an update\",\"authors\":\"Jeesun Yoon, Do-Youn Oh\",\"doi\":\"10.1038/s41571-024-00924-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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. Anti-HER2 therapy has revolutionized the treatment of HER2-positive breast cancer. However, HER2 has emerged as a driver of various other cancers and the indications for HER2-targeted therapy have expanded to include diverse HER2-overexpressing as well as HER2-mutant tumour types beyond breast cancer, facilitated by the advent of novel agents with greater potency and distinct mechanisms of action. Some of these agents have demonstrated promising activity even against HER2-low cancers. Herein, Yoon and Oh describe the landscape of HER2 alterations and HER2-targeted drug development beyond breast cancer. They also discuss new insights into mechanisms of resistance and potential strategies by which they might be overcome.\",\"PeriodicalId\":19079,\"journal\":{\"name\":\"Nature Reviews Clinical Oncology\",\"volume\":\"21 9\",\"pages\":\"675-700\"},\"PeriodicalIF\":81.1000,\"publicationDate\":\"2024-07-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Reviews Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41571-024-00924-9\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41571-024-00924-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

受体酪氨酸激酶 HER2(又称 ErbB2)是乳腺癌或胃癌患者的公认治疗靶点,这些患者是根据免疫组化的 HER2 过度表达和/或原位杂交的 ERBB2 扩增而被选中的。随着癌症分子图谱分析技术的进步以及精准医疗方法在肿瘤学实践中的广泛应用,实体瘤中可操作的HER2改变已扩展到传统的HER2过表达和ERBB2扩增之外的ERBB2突变。除乳腺癌和胃癌外,实体瘤中还可发现这些不同的 HER2 改变,但针对其他肿瘤类型的 HER2 靶向治疗方案却寥寥无几。尽管如此,自本刊发表上一篇有关该主题的综述以来的 5 年间,HER2 靶向疗法的开发取得了明显而丰硕的进展,包括新的疾病适应症、具有不同作用机制的创新药物以及监管机构审批的新框架。这些进展的最终结果是,抗 HER2 抗体-药物共轭物曲妥珠单抗(trastuzumab deruxtecan)最近通过组织学诊断获得批准,用于治疗 HER2 表达异常的实体瘤患者。在这篇新的《综述》中,我们将介绍目前除乳腺癌以外的 HER2 靶向疗法的最新发展情况,以及未来预期的 HER2 靶向治疗策略,以克服耐药性,从而改善疗效和患者预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

HER2-targeted therapies beyond breast cancer — an update

HER2-targeted therapies beyond breast cancer — an update

HER2-targeted therapies beyond breast cancer — an update
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. Anti-HER2 therapy has revolutionized the treatment of HER2-positive breast cancer. However, HER2 has emerged as a driver of various other cancers and the indications for HER2-targeted therapy have expanded to include diverse HER2-overexpressing as well as HER2-mutant tumour types beyond breast cancer, facilitated by the advent of novel agents with greater potency and distinct mechanisms of action. Some of these agents have demonstrated promising activity even against HER2-low cancers. Herein, Yoon and Oh describe the landscape of HER2 alterations and HER2-targeted drug development beyond breast cancer. They also discuss new insights into mechanisms of resistance and potential strategies by which they might be overcome.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
99.40
自引率
0.40%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Nature Reviews publishes clinical content authored by internationally renowned clinical academics and researchers, catering to readers in the medical sciences at postgraduate levels and beyond. Although targeted at practicing doctors, researchers, and academics within specific specialties, the aim is to ensure accessibility for readers across various medical disciplines. The journal features in-depth Reviews offering authoritative and current information, contextualizing topics within the history and development of a field. Perspectives, News & Views articles, and the Research Highlights section provide topical discussions, opinions, and filtered primary research from diverse medical journals.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信