Breast cancer is the most common cancer and the most important cause of cancer-related death in females worldwide. Antibody–drug conjugates (ADCs) represent a novel class of targeted therapies that combine the precision of monoclonal antibodies with the potent cell-killing activity of cytotoxic drugs. This review highlights recent mechanistic, technological, and clinical developments of ADCs in breast cancer, including next-generation ADCs beyond those that target HER2 (human epidermal growth factor receptor 2). Authors performed a systematic literature study for ADCs and their structural features, including their components (antibody, linker, and payload) and their therapeutic efficacy. A frame of preclinical research findings and clinical evidence integration of HER2-targeted therapy outcomes in HER2-positive, HER2-low, and triple-negative breast cancer (TNBC) subtypes were presented. Clinical studies of antibody–drug conjugates such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan have demonstrated significant improvements in progression-free survival and overall survival across diverse breast cancer patient populations. ADCs offer unique advantages in breast cancer therapy by combining the precision of targeted antibodies with the potency of chemotherapy drugs. This allows them to selectively kill cancer cells, overcome resistance, reduce toxicity to healthy tissues, and expand treatment options for difficult subtypes like HER2-low and triple-negative breast cancer. Unlike previous reviews focusing on HER2-targeted ADCs, herein we review exciting ADCs targeting HER3 HER3 (human epidermal growth factor receptor 3) and Nectin-4, as well as the implications of bispecific and immune-stimulatory ADCs in the clinic. Additionally, it features mechanism-based innovations and novel trial data that revolutionize ADC applications in the HER2-low as well as the triple-negative breast cancer subtypes. The advent of ADC is changing precision oncology in breast cancer. With a new design and indications evolving, they are an attractive avenue for bypassing resistance and reducing toxicity and ultimately improving patient outcomes in the molecular subtypes. The present review summarizes recent advancements in antibody–drug conjugates (ADCs) and emerging targeted therapeutic strategies for breast cancer. It covers mechanistic insights, linker–payload innovations, receptor-based targeting approaches, clinical trial progress, and next-generation modalities that extend beyond HER2-directed ADCs. Current challenges, safety profiles, and future opportunities in engineering more selective and effective ADC platforms are also discussed.
乳腺癌是全球女性最常见的恶性肿瘤，也是导致癌症相关死亡的首要原因。抗体偶联药物（ADCs）作为一类新型靶向疗法，将单克隆抗体的精准靶向性与细胞毒性药物的高效杀伤力相结合。本综述重点阐述ADCs在乳腺癌领域的最新机制研究、技术进展与临床发展，包括超越人表皮生长因子受体2（HER2）靶向的新一代ADCs。作者系统梳理了ADCs及其结构特征的相关文献，涵盖其组成成分（抗体、连接子、载荷药物）及治疗效能。研究构建了涵盖HER2阳性、HER2低表达及三阴性乳腺癌（TNBC）亚型的临床前研究证据与HER2靶向治疗临床结果的整合分析框架。曲妥珠单抗-美坦新偶联物（T-DM1）、曲妥珠单抗-德鲁替康偶联物（T-DXd）以及戈沙妥珠单抗等抗体偶联药物的临床研究显示，其在多种乳腺癌患者群体中能显著改善无进展生存期和总生存期。ADCs通过融合靶向抗体的精准性与化疗药物的强效性，在乳腺癌治疗中展现出独特优势：可选择性杀伤癌细胞、克服耐药性、降低对健康组织的毒性，并为HER2低表达及三阴性乳腺癌等难治亚型拓展治疗选择。与既往聚焦HER2靶向ADCs的综述不同，本文还探讨了靶向人表皮生长因子受体3（HER3）及Nectin-4的新型ADCs，以及双特异性与免疫刺激型ADCs的临床价值。此外，本文重点分析了基于作用机制的创新策略与革新HER2低表达及三阴性乳腺癌亚型ADC应用的新型试验数据。ADC的出现正在重塑乳腺癌精准治疗格局。随着新型药物设计与适应症的不断发展，ADCs为克服耐药、降低毒性并最终改善不同分子亚型患者的预后提供了极具前景的治疗途径。本综述系统总结了抗体偶联药物（ADCs）的最新进展及乳腺癌新兴靶向治疗策略，涵盖作用机制解析、连接子-载荷系统创新、基于受体的靶向策略、临床试验进展以及超越HER2靶向的下一代治疗模式，并对当前挑战、安全性特征及开发更具选择性与有效性ADC平台的未来方向进行了探讨。
Antibody–Drug Conjugates and Beyond: Next-Generation Targeted Therapies for Breast Cancer
肿瘤(癌症)患者之家