Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.

抗体药物偶联物 (ADC) 是一类新型靶向癌症疗法，能够使用与细胞毒性有效负载连接的单克隆抗体选择性地将细胞毒性药物递送至肿瘤细胞。与标准化疗相比，ADC 技术具有肿瘤特异性、提高疗效并降低毒性。与 ADC 使用相关的常见毒性包括眼、肺、血液和神经毒性。美国食品和药物管理局 (FDA) 已批准多种 ADC 用于治疗复发性或转移性妇科癌症患者，这些患者的预后较差且有效的治疗选择有限。FDA 批准的第一个用于治疗复发性或转移性宫颈癌的 ADC 是 tisotumab vedotin，一种组织因子靶向药物，在 innovaTV 204 试验中显示出反应。Mirvetuximab soravtansine 以叶酸受体 α 为靶点，根据 SORAYA 试验的结果，被批准用于叶酸受体 α 阳性、铂耐药的上皮性卵巢癌患者。虽然尚无 FDA 批准用于治疗子宫癌的 ADC，但抗人表皮生长因子受体 2 (HER2) 药物曲妥珠单抗 deruxtecan 正在积极研究中。在本次综述中，我们将描述 ADC 的结构和作用机制，讨论其毒性特征，综述用于治疗妇科癌症的已批准和正在研究的 ADC，并讨论 ADC 耐药机制。