New Life of Topoisomerase I Inhibitors as Antibody–Drug Conjugate Warheads

Summary Antibody–drug conjugates (ADC) allow the delivery of cytotoxic chemotherapeutic agents to tumors. Two ADC delivering topoisomerase I (TOP1) poisons (Enhertu and Trodelvy) have recently been FDA-approved for Her2- and Trop2-expressing solid tumors. In a recent study, a TOP1-anti B7-H4 ADC was described and shown to be synergistic with a novel PARP1-selective inhibitor. See related article by Kinneer et al., p. 1086