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Anthracyclines

  • Chapter
Cancer Therapeutics

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

Abstract

The clinical activity of actinomycin D against Wilm’s pediatric kidney tumor and choriocarcinoma in the early to mid-1950s resulted in a widespread effort to discover other antibiotic substances for potential use in the treatment of malignancies. As a result, cancer chemotherapy was altered immeasurably more than 30 years ago by the independent discoveries by Grein (1), Dubost (2), and their colleagues of an anthracycline antibiotic, derived from a Streptomyces soil mold, with significant experimental activity against leukemias. Structurally this intensely red product whose common name, daunorubicin, reflects both its Italian (daunomicina) and French (rubidomycine) origins, consists of a planar anthraquinone attached to a daunosamine sugar; the latter has been shown to stabilize intercalation of the molecule with DNA, which for many years was considered to be the principal mechanism of anthracycline action (3). Subsequently, although not necessarily through DNA interaction, this structural requirement has proven essential for the multiple potential mechanisms of action now identified for anthracyclines, including inhibition of DNA topoisomerase I (4) and II (5), inhibition of helicases (6), generation of toxic free radicals (7), alteration of membrane structure and function (8–10), and endonucleolytic cleavage (11).

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Authors
  1. Trevor W. Sweatman PhD
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  2. Mervyn Israel PhD
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  1. Dana-Farber Cancer Institute, Boston, MA, USA

    Beverly A. Teicher

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Sweatman, T.W., Israel, M. (1997). Anthracyclines. In: Teicher, B.A. (eds) Cancer Therapeutics. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-717-8_5

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  • DOI: https://doi.org/10.1007/978-1-59259-717-8_5

  • Publisher Name: Humana Press, Totowa, NJ

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