{"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. 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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.
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.