He Jinhui, Chen Mi, Jia Li, Wang Ying
Affiliated Hospital of Chengdu University, Chengdu Seventh People's Hospital, Department of Obstetrics and Gynecology, Chengdu, China.
The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, China.
Int J Gynecol Cancer. 2025 Sep;35(9):101978. doi: 10.1016/j.ijgc.2025.101978. Epub 2025 Jun 19.
Antibody-drug conjugates (ADCs) are an emerging class of targeted therapies that combine monoclonal antibodies with potent cytotoxic payloads, demonstrating significant potential in the treatment of gynecologic malignancies. By selectively targeting tumor-associated antigens, ADCs enable precise drug delivery while minimizing off-target toxicity. Currently, mirvetuximab soravtansine and tisotumab vedotin have been approved by the Food and Drug Administration for the treatment of folate receptor-alpha-positive, platinum-resistant ovarian cancer and recurrent cervical cancer, respectively, exhibiting promising objective response rates and manageable toxicity profiles in pivotal clinical trials. However, ADC therapy faces challenges, including ocular toxicity, pulmonary toxicity, peripheral neuropathy, tumor antigen heterogeneity, and acquired resistance. Additionally, multiple investigational ADCs, such as upifitamab rilsodotin (targeting NaPi2b), trastuzumab deruxtecan (targeting HER2), and sacituzumab govitecan (targeting trophoblast cell surface antigen 2), have demonstrated preliminary efficacy in ongoing clinical trials, offering new therapeutic opportunities for gynecologic malignancies. This review comprehensively summarizes the current clinical applications and research progress of ADCs in gynecologic cancers, including key clinical trials, therapeutic efficacy, safety profiles, and associated challenges. Furthermore, we discuss future optimization strategies, including the identification of novel targets, rational combination therapies, and molecular design improvements to advance ADC-based precision treatment in gynecologic oncology.
抗体药物偶联物（ADCs）是一类新兴的靶向治疗药物，它将单克隆抗体与强效细胞毒性药物结合，在妇科恶性肿瘤治疗中显示出巨大潜力。通过选择性地靶向肿瘤相关抗原，ADCs能够实现精确的药物递送，同时将脱靶毒性降至最低。目前，mirvetuximab soravtansine和tisotumab vedotin已分别获得美国食品药品监督管理局批准，用于治疗叶酸受体-α阳性、铂耐药卵巢癌和复发性宫颈癌，在关键临床试验中展现出了有前景的客观缓解率和可管理的毒性特征。然而，ADC治疗面临诸多挑战，包括眼部毒性、肺部毒性、周围神经病变、肿瘤抗原异质性和获得性耐药。此外，多种处于研究阶段的ADCs，如upifitamab rilsodotin（靶向NaPi2b）、曲妥珠单抗德鲁替康（靶向HER2）和戈沙妥珠单抗（靶向滋养层细胞表面抗原2），在正在进行的临床试验中已显示出初步疗效，为妇科恶性肿瘤提供了新的治疗机会。本综述全面总结了ADCs在妇科癌症中的当前临床应用和研究进展，包括关键临床试验、治疗效果、安全性概况及相关挑战。此外，我们还讨论了未来的优化策略，包括新型靶点的鉴定、合理的联合治疗以及分子设计改进，以推进基于ADC的妇科肿瘤精准治疗。
