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

Clin Cancer Res. 2023 Mar 14;29(6):991-993. doi: 10.1158/1078-0432.CCR-22-3640.

Abstract

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.

Publication types

  • Editorial
  • Research Support, N.I.H., Intramural
  • Comment

MeSH terms

  • Humans
  • Immunoconjugates* / pharmacology
  • Immunoconjugates* / therapeutic use
  • Neoplasms* / drug therapy
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Topoisomerase I Inhibitors / pharmacology
  • Topoisomerase I Inhibitors / therapeutic use

Substances

  • Topoisomerase I Inhibitors
  • AZD5305
  • Immunoconjugates
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1