Nerone Marta, Grande Maria Del, Sessa Cristiana, Colombo Ilaria
Service of Medical Oncology, Oncology Institute of Southern Switzerland (IOSI), EOC, 6500 Bellinzona, Switzerland.
Explor Target Antitumor Ther. 2022;3(2):149-171. doi: 10.37349/etat.2022.00077. Epub 2022 Apr 19.
Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents. These drugs have been extensively studied both in solid and hematologic malignancies, leading to substantial improvement in the therapeutic landscape for several tumors. Despite no ADC have been yet approved for the treatment of gynecological malignancies, some agents have shown promising results and might have the potential to become part of the standard of care. Among them, mirvetuximab soravtansine has shown activity in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent and in combination. Tisotumab vedotin is active in patients with pre-treated cervical cancer, and further investigation is ongoing. The purpose of this review is to summarize the structural and functional characteristics of ADCs and analyze the most recent and promising data regarding the clinical development of ADCs in gynecological malignancies. The available data on the efficacy of the more studied ADCs in ovarian, endometrial, and cervical cancers will be discussed along with toxicities of special interest, the mechanisms of resistance, and future possible drugs combination.
抗体药物偶联物（ADCs）是一类新型治疗药物，旨在靶向肿瘤细胞上的特定抗原，将单克隆抗体的特异性与经典化疗药物的细胞毒性相结合。这些药物在实体瘤和血液系统恶性肿瘤中均得到了广泛研究，使多种肿瘤的治疗前景有了显著改善。尽管尚无ADC获批用于治疗妇科恶性肿瘤，但一些药物已显示出有前景的结果，可能有潜力成为标准治疗方案的一部分。其中，mirvetuximab soravtansine在叶酸-α受体高表达的铂耐药卵巢癌中作为单药及联合用药均显示出活性。Tisotumab vedotin在预处理过的宫颈癌患者中具有活性，进一步的研究正在进行中。本综述的目的是总结ADCs的结构和功能特征，并分析ADCs在妇科恶性肿瘤临床开发方面最新且有前景的数据。将讨论在卵巢癌、子宫内膜癌和宫颈癌中研究较多的ADCs的疗效相关现有数据，以及特别关注的毒性、耐药机制和未来可能的药物联合。
