Abstract：
Antibody-drug conjugates (ADCs)-a groundbreaking class of agents for targeted oncological therapies-consist of monoclonal antibodies with strong antigenic specificity coupled with highly active cytotoxic agents (also referred to as \"payloads\"). Over the past 2 decades, breast cancer research has evolved into a focal point for the research and development of ADCs, leading to several recent landmark publications. These advancements are ushering in a transformative era in breast cancer treatment and redefining conventional classifications by introducing a prospective subtype termed \"HER2-low.\" The latest iterations of ADCs have demonstrated enhanced efficacy in disease management through the optimization of various factors, notably the incorporation of the bystander effect. These conjugates are no longer limited to the oncogenic driver human epidermal growth factor receptor 2 (HER2). Other antigens, including human epidermal growth factor receptor 3 (HER3), trophoblast cell surface antigen 2 (Trop-2), zinc transporter ZIP6 (LIV-1), and folate receptor α (FRα), have recently emerged as intriguing tumor cell surface nondriver gene targets for ADCs, each with one or more specific ADCs that showed encouraging results in the breast cancer field. This article reviews recent advances in the application of ADCs in the treatment of HER2-low breast cancer. Additionally, this review explores the underlying factors contributing to the impact of target selection on ADC efficacy to provide new insights for optimizing the clinical application of ADCs in individuals with low HER2 expression in advanced breast cancer.
摘要：
抗体-药物缀合物(ADC)-用于靶向肿瘤治疗的一类突破性药物-由具有强抗原特异性的单克隆抗体与高活性细胞毒性剂(也称为“有效载荷”)组成。在过去的20年里,乳腺癌研究已经发展成为ADC研究和开发的焦点，最近出版了几本具有里程碑意义的出版物。这些进步正在开创乳腺癌治疗的变革时代，并通过引入称为“HER2-low”的前瞻性亚型来重新定义常规分类。“ADC的最新迭代显示，通过优化各种因素，提高了疾病管理的功效，特别是纳入旁观者效应。这些缀合物不再限于致癌驱动人表皮生长因子受体2(HER2)。其他抗原，包括人类表皮生长因子受体3（HER3），滋养层细胞表面抗原2（Trop-2），锌转运蛋白ZIP6（LIV-1），和叶酸受体α（FRα），最近出现了有趣的肿瘤细胞表面非驱动基因靶标的ADC，每个都有一个或多个特定的ADC，在乳腺癌领域显示出令人鼓舞的结果。本文就近年来ADCs在HER2-low乳腺癌治疗中的应用进展作一综述。此外,本综述探讨了影响靶点选择对ADC疗效影响的潜在因素,为优化晚期乳腺癌HER2低表达个体ADC的临床应用提供新的见解.
