Antibody–drug conjugates for advanced/recurrent high-grade endometrial cancer: potential targets, strategies and challenges

Abstract

The incidence of endometrial cancer is on the rise, along with a concurrent increase in mortality. For advanced-stage endometrial cancer, standard treatment regimens include surgery, radiation, and cytotoxic chemotherapy; however, options are limited in the recurrent disease setting. Antibody–drug conjugates (ADCs) have emerged as a potent therapeutic option for patients who have experienced progression with chemotherapy, immunotherapy, or targeted therapy. Compared with conventional chemotherapy, ADCs deliver more potent cytotoxic payloads to the tumor by linking them to antibodies that target specific antigens preferentially expressed on malignant cells. Despite this advantage, resistance to ADCs has also emerged. Thus, it is important to understand the mechanisms of resistance and how they might be overcome to impact clinical outcomes. This review summarizes the current clinical application and ongoing development of ADCs in endometrial cancer, including evidence from preclinical studies and early-phase clinical trials, and discusses future challenges and directions.