Advances in Antibody-Drug Conjugates for Endometrial Cancer.

Abstract

The treatment of advanced endometrial cancer is clinically challenging, prompting the exploration of innovative therapeutic strategies such as antibody-drug conjugates (ADC). ADCs, which include mAbs, cytotoxic components, and linkers, demonstrate robust targeting, cytotoxicity, and manageable adverse effects. To provide a thorough understanding of the status of research, this review elucidates promising therapeutic targets in endometrial cancer, such as HER2, folate receptor α, and trophoblast surface antigen-2, and summarizes preclinical and clinical trial data on related ADC drugs in endometrial cancer. We also discuss the toxicity of ADC drugs. Most adverse events arise from cytotoxic components such as microtubule inhibitors and topoisomerase inhibitors. The ocular toxicity may be mainly related to off-target effects of monomethyl auristatin F/DF4 payloads. Interstitial lung disease is a serious adverse event, mainly caused by antibodies, and most of them are of grade 1 to 2 toxicity. Among them, anti-HER2 ADC-induced interstitial pneumonia is commonly dose-dependent. Moreover, we identified potential new targets for endometrial cancer treatment and explored strategies to overcome ADC resistance, such as choosing combination therapy or developing a new generation of ADC drugs. Continuous research and innovation in this field hold promise for improving the survival and overall quality of life of patients with advanced endometrial cancer.