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Mechanism of Action of Topoisomerase 1 Poisons

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Camptothecins in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

DNA topoisomerases are important nuclear enzymes involved in many aspects of DNA metabolism, such as DNA replication, RNA transcription, chromosome condensation, and segregation (1–5). They perform their topological transformation reactions on DNA via a concerted breakage/religation mechanism (4,6–8). Because of their delicate act on DNA, topoisomerases can be double-edged swords. It is now well established that many xenobiotics, DNA lesions, and physiological stresses (e.g., oxidative stress, acidic pH stress, thiol stress) can interfere with the breakage/religation reactions of topoisomerases, resulting in topoisomerase-mediated DNA damage (9–14). Among the five human DNA topoisomerases (hTOP1, hTOP2α, hTOP2β, hTOP3α, and hTOP3β), the first three have been identified to be molecular targets of anticancer drugs (1,9,11,15–22).

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Authors and Affiliations

  1. Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ

    Leroy F. Liu PhD & Shyamal D. Desai PhD

  2. Cancer Institute of New Jersey, New Brunswick, NJ

    Leroy F. Liu PhD

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  1. Leroy F. Liu PhD
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  2. Shyamal D. Desai PhD
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Editors and Affiliations

  1. Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY

    Val R. Adams PharmD

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  3. Experimental Therapeutics Program, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  4. Tigen Pharmaceuticals Inc., Lexington, KY

    Thomas G. Burke PhD

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Liu, L.F., Desai, S.D. (2005). Mechanism of Action of Topoisomerase 1 Poisons. In: Adams, V.R., Burke, T.G. (eds) Camptothecins in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-866-8:003

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  • DOI: https://doi.org/10.1385/1-59259-866-8:003

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