Antibody-drug conjugates in gynecologic cancer: current landscape, clinical data, and emerging targets

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.