Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients.

IF 4.7 2区 医学 Q2 ONCOLOGY
Current Treatment Options in Oncology Pub Date : 2025-04-01 Epub Date: 2025-03-08 DOI:10.1007/s11864-025-01300-0
Lijuan He, Ben Liu, Zhuanfang Wang, Qinying Han, Hao Chen
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引用次数: 0

Abstract

Opinion statement: Gastric cancer (GC) is a deadly disease worldwide, and trastuzumab in combination with chemotherapy has been the standard first-line treatment for HER2-positive GC following the TOGA trial. Besides adjuvant therapy, HER2-directed therapy is widely used as neoadjuvant or translational therapy, and survival benefit even surgical opportunities is seen in these patients. However, resistance is not rare in recent years, and the second-line treatment for trastuzumab beyond progression has received widespread attention in GC. Moreover, current evidence cannot recommend trastuzumab for patients with IHC1+ HER2 low expression GC yet. Researchers are currently investigating whether GC patients with low HER2 expression could also benefit from HER2-directed therapies. In addition to using HER2 as a target for targeted therapy, HER2-mediated targeted delivery of cytotoxic drugs and targeted immunity have made important contributions to overcoming trastuzumab resistance in recent trials. HER2/neu-derived peptide epitopes vaccination and HER2-specific chimeric antigen receptor (CAR) therapy focus on reestablishing anti-tumor immunity in different ways and show significant anti-tumor activity. Other antibodies that target different regions of the HER2 receptor or block key downstream pathways such as AKT or PI3K also offer potential anti-tumor activity against HER2. HER2 use in GC will not be hampered by resistance or low expression and will play a bigger role. We review the current efforts to enable GC patients with trastuzumab-resistant and HER2 low-expressing accessible to HER2 targeted therapy and present our consideration for future HER2 in GC.

针对胃癌患者的 HER2 靶向疗法不断发展。
观点声明:胃癌(GC)是世界范围内的一种致命疾病,在TOGA试验之后,曲妥珠单抗联合化疗已成为her2阳性胃癌的标准一线治疗。除辅助治疗外,her2定向治疗被广泛用作新辅助或转化治疗,这些患者的生存获益甚至手术机会。然而,近年来耐药并不罕见,曲妥珠单抗进展后的二线治疗在胃癌中受到了广泛关注。此外,目前的证据还不能推荐曲妥珠单抗用于IHC1+ HER2低表达GC患者。研究人员目前正在研究HER2低表达的胃癌患者是否也能从HER2定向治疗中获益。除了使用HER2作为靶向治疗的靶标外,HER2介导的细胞毒性药物靶向递送和靶向免疫在最近的试验中为克服曲妥珠单抗耐药做出了重要贡献。HER2/新衍生肽表位疫苗和HER2特异性嵌合抗原受体(CAR)治疗侧重于以不同的方式重建抗肿瘤免疫,并显示出显著的抗肿瘤活性。其他针对HER2受体不同区域或阻断关键下游通路(如AKT或PI3K)的抗体也具有潜在的抗HER2肿瘤活性。HER2在GC中的应用不会受到抵抗或低表达的阻碍,将发挥更大的作用。我们回顾了目前的努力,使曲妥珠单抗耐药和HER2低表达的胃癌患者能够接受HER2靶向治疗,并提出了我们对未来HER2在胃癌中的考虑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.10
自引率
0.00%
发文量
113
审稿时长
>12 weeks
期刊介绍: This journal aims to review the most important, recently published treatment option advances in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to facilitate worldwide approaches to cancer treatment. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as endocrine tumors, lymphomas, neuro-oncology, and cancers of the breast, head and neck, lung, skin, gastrointestinal tract, and genitourinary region. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. We also provide commentaries from well-known oncologists, and an international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research.
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