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The Potential of Topoisomerase Inhibitor-Based Antibody-Drug Conjugates.

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.

SUBMITTER: Han S

PROVIDER: S-EPMC9413092 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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The Potential of Topoisomerase Inhibitor-Based Antibody-Drug Conjugates.

Han Seungmin S Lim Kwang Suk KS Blackburn Brody J BJ Yun Jina J Putnam Charles W CW Bull David A DA Won Young-Wook YW

Pharmaceutics 20220816 8

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) ha ...[more]

PMID: 36015333

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Dataset Information

The Potential of Topoisomerase Inhibitor-Based Antibody-Drug Conjugates.

Publications

The Potential of Topoisomerase Inhibitor-Based Antibody-Drug Conjugates.

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