Zhu Kunrui, Yang Xinyi, Tai Hebei, Zhong Xiaorong, Luo Ting, Zheng Hong
Institute for Breast Health Medicine, Cance Center, Breast Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
College of Clinical Medical, Guizhou Medical University, Guiyang, 550000, Guizhou Province, China.
Biomark Res. 2024 Feb 2;12(1):16. doi: 10.1186/s40364-024-00565-1.
Abnormal alterations in human epidermal growth factor receptor 2 (HER2, neu, and erbB2) are associated with the development of many tumors. It is currently a crucial treatment for multiple cancers. Advanced in molecular biology and further exploration of the HER2-mediated pathway have promoted the development of medicine design and combination drug regimens. An increasing number of HER2-targeted drugs including specific monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs) have been approved by the U.S. Food and Drug Administration. The emergence of ADCs, has significantly transformed the treatment landscape for various tumors, such as breast, gastric, and bladder cancer. Classic monoclonal antibodies and novel TKIs have not only demonstrated remarkable efficacy, but also expanded their indications, with ADCs in particular exhibiting profound clinical applications. Moreover the concept of low HER2 expression signifies a breakthrough in HER2-targeted therapy, indicating that an increasing number of tumors and patients will benefit from this approach. This article, provides a comprehensive review of the underlying mechanism of action, representative drugs, corresponding clinical trials, recent advancements, and future research directions pertaining to HER2-targeted therapy.
人表皮生长因子受体2（HER2、neu和erbB2）的异常改变与多种肿瘤的发生发展相关。它目前是多种癌症的关键治疗方法。分子生物学的进展以及对HER2介导途径的进一步探索推动了药物设计和联合用药方案的发展。越来越多的HER2靶向药物，包括特异性单克隆抗体、酪氨酸激酶抑制剂（TKIs）和抗体药物偶联物（ADCs）已获美国食品药品监督管理局批准。ADCs的出现显著改变了各种肿瘤（如乳腺癌、胃癌和膀胱癌）的治疗格局。经典单克隆抗体和新型TKIs不仅显示出显著疗效，还扩大了其适应证，尤其是ADCs展现出了深刻的临床应用价值。此外，低HER2表达的概念标志着HER2靶向治疗的一项突破，表明越来越多的肿瘤和患者将从这种治疗方法中受益。本文对HER2靶向治疗的作用机制、代表性药物、相应临床试验、最新进展以及未来研究方向进行了全面综述。
