The Potential of Topoisomerase Inhibitor-Based Antibody–Drug Conjugates

Seungmin Han, Kwang Suk Lim, Brody J. Blackburn, Jina Yun, Charles W. Putnam, David A. Bull, Young Wook Won

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


DNA topoisomerases are essential enzymes that stabilize DNA supercoiling and resolve entanglements. Topoisomerase inhibitors have been widely used as anti-cancer drugs for the past 20 years. Due to their selectivity as topoisomerase I (TOP1) inhibitors that trap TOP1 cleavage complexes, camptothecin and its derivatives are promising anti-cancer drugs. To increase accumulation of TOP1 inhibitors in cancer cells through the targeting of tumors, TOP1 inhibitor antibody–drug conjugates (TOP1-ADC) have been developed and marketed. Some TOP1-ADCs have shown enhanced therapeutic efficacy compared to prototypical anti-cancer ADCs, such as T-DM1. Here, we review various types of camptothecin-based TOP1 inhibitors and recent developments in TOP1-ADCs. We then propose key points for the design and construction of TOP1-ADCs. Finally, we discuss promising combinatorial strategies, including newly developed approaches to maximizing the therapeutic potential of TOP1-ADCs.

Original languageEnglish (US)
Article number1707
Issue number8
StatePublished - Aug 2022


  • anti-cancer drug
  • antibody–drug conjugates
  • targeted drug delivery
  • topoisomerase 1
  • topoisomerase inhibitor

ASJC Scopus subject areas

  • Pharmaceutical Science


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