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Models for Studying the Action of Topoisomerase-I Targeted Drugs

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Tumor Models in Cancer Research

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

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Abstract

Many of the cytotoxic drugs that are active in the curative or palliative treatment of human cancers are now known to mediate their effects through interaction with DNA topoisomerases stabilizing covalent DNA-protein intermediates. The epipodophylotoxins, anthracyclines, anthrapyrazoles, and actinomycins appear to target topoisomerase II, whereas drugs of the camptothecin class work specifically through their interaction with topoisomerase I. Some, such as actinomycin D, certain rebeccamycin analogs, and a new class of ethylidene glucoside-epipodophyllotoxins, may be dual-topoisomerase inhibitors (1). The clinical utility of the epipodophyllotoxin, etoposide, and the anthracyclines doxorubicin, daunorubicin, and actinomycin D have been well-established (2). The spectrum of utility of camptothecin drugs in treatment of human cancer also remains to be determined. However, current results from clinical trials suggest that drugs that target topoisomerase I may represent novel agents with considerable activity in a relatively broad spectrum of malignancies.

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Authors
  1. Joyce Thompson MD
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  2. Clinton F. Stewart PharmD
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  3. Peter J. Houghton PhD
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Editors and Affiliations

  1. Lilly Research Laboratories, Indianapolis, IN, USA

    Beverly A. Teicher

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Thompson, J., Stewart, C.F., Houghton, P.J. (2002). Models for Studying the Action of Topoisomerase-I Targeted Drugs. In: Teicher, B.A. (eds) Tumor Models in Cancer Research. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-100-8_29

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  • DOI: https://doi.org/10.1007/978-1-59259-100-8_29

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-6883-1

  • Online ISBN: 978-1-59259-100-8

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