创新链/学科链/研发链/产业链

新药研发前沿动态 / 医药领域趋势进展

HER2低表达晚期乳腺癌抗体药物偶联物研究进展

Research Progress of Antibody-Drug Conjugates for HER2 Low Expression Advanced Breast Cancer

  • 摘要: 抗体药物偶联物(ADCs)是由具有抗原特异性的单克隆抗体和高活性细胞毒性载荷偶联而成的一种突破性肿瘤靶向治疗药物。近年来ADCs不再局限于以驱动基因如人类表皮生长因子受体2(HER2)为靶点,人类表皮生长因子受体3(HER3)、滋养层细胞表面抗原-2(Trop-2)和叶酸受体ɑ(FRɑ)等肿瘤细胞表面非驱动基因为靶点的ADCs不断涌现。目前ADCs药物在乳腺癌领域已取得较大进展,并引入“HER2低表达”的前瞻性亚型重新定义了传统的乳腺癌分型,正在彻底改变乳腺癌的治疗格局。新靶点的探索扩大了从ADCs中受益的患者比例,尤其是HER2低表达乳腺癌也可从ADCs治疗中获益。综述重点探讨了ADCs药物在治疗HER2低表达晚期乳腺癌中的应用进展,为优化ADCs药物在晚期HER2低表达乳腺癌患者中的临床应用提出新的展望。

     

    Abstract: Antibody-drug conjugates(ADCs), which consist of monoclonal antibodies with strong antigenic specificity, coupled with highly active cytotoxic agents(also referred to as “payloads”), represent a groundbreaking class of targeted oncological therapy. These conjugates are no longer limited to oncogenic driver human epidermal growth factor receptor 2(HER2) as a target. Other antigens, including human epidermal growth factor receptor 3(HER3), trophoblast cell surface antigen 2(Trop-2), and folate receptor ɑ(FRɑ), have recently emerged as tumor cell surface non-oncodriver gene targets for ADCs. At present, significant advancements have been achieved in the field of breast cancer due to the emergence of ADCs. Moreover, the identification of the prospective subtype "HER2-low" has redefined conventional classification of breast cancer, thereby revolutionizing the treatment approach for this disease. Exploration of new targets is critical to expand the fraction of patients who can benefit from ADCs. Furthermore, ADCs are showing promise in addressing HER2-low breast cancer cases. This article reviews the research progress in the application of ADCs in the treatment of advanced HER2-low breast cancer in recent years, and puts forward new prospects for the future treatment of HER2-low advanced breast cancer.

     

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