GYNECOLOGIC CANCER: Edited by Gottfried E. KonecnyNovel antibody–drug conjugates: current and future roles in gynecologic oncologyTymon-Rosario, Joan; Zeybek, Burak; Santin, Alessandro D. Author Information Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA Correspondence to Alessandro D. Santin, MD, Department of Obstetrics, Gynecology, and Reproductive Sciences; Co-Chief Gynecologic Oncology, Yale School of Medicine, LSOG Bld. Room 305, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA. Tel: +1 203 737 4450; fax: +1 203 737 4339; e-mail: [email protected] Current Opinion in Obstetrics and Gynecology: February 2021 - Volume 33 - Issue 1 - p 26-33 doi: 10.1097/GCO.0000000000000642 Buy Metrics Abstract Purpose of review Antibody–drug conjugates (ADCs) represent a new class of drugs that combine a surface receptor-targeting antibody linked to a cytotoxic molecule. This review summarizes the current literature demonstrating their tremendous promise as therapeutic agents in the treatment of aggressive gynecologic malignancies. Recent findings Several antigens have proven to be differentially overexpressed in a variety of gynecologic tumors when compared with normal surrounding tissue and serve as novel targets for ADC therapy. In the last few years HER2/neu, folic acid-alpha (FRα) and Trop-2 overexpression have been exploited as excellent targets by novel ADCs such as Trastuzumab emtansine (T-DM1), SYD985, IMGN853 (Mirvetuximab soravtansine) and Sacituzumab govitecan (SG, IMMU-132) in multiple tumors including ovarian, endometrial and cervical cancers. Although the selectivity of ADCs with noncleavable linkers (i.e. T-DM1) has shown negligible effect on surrounding antigen negative cells, those ADCs with cleavable linkers (i.e. SYD985, IMGN853 and SG) may kill both antigen-positive target cells and surrounding antigen-negative cells via the bystander effect. Summary Preclinical data strongly supports these ADCs and ongoing clinical trials will shed further light into the potential of making these drugs part of current standard practice and providing our patients with a higher level of personalized cancer care. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.