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- Title
The Potential of Topoisomerase Inhibitor-Based Antibody–Drug Conjugates.
- Authors
Han, Seungmin; Lim, Kwang Suk; Blackburn, Brody J.; Yun, Jina; Putnam, Charles W.; Bull, David A.; Won, Young-Wook
- Abstract
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.
- Subjects
ANTIBODY-drug conjugates; DNA topoisomerase I; DNA topoisomerases; ANTINEOPLASTIC agents; TREATMENT effectiveness; THERAPEUTICS
- Publication
Pharmaceutics, 2022, Vol 14, Issue 8, p1707
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics14081707