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Prodrugs of Anthracyclines in Cancer Chemotherapy

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Designing and developing truly tumor-specific prodrugs remains a challenge in the field of cancer chemotherapy. Active targeting strategies, on the one hand, aim at exploiting membrane-associated receptors or antigens for drug delivery; on the other hand, the enhanced vascular permeability and retention of macromolecules in tumor tissue substantiates the concept of passive targeting. Consequently, research efforts have concentrated on conjugating anticancer agents with a wide spectrum of carriers including antibodies, peptides, serum proteins, and synthetic polymers. Conversely, low-molecular weight prodrugs of anticancer agents have been developed that do not bear an active or passive targeting moiety, but are activated by tumorassociated enzymes at the tumor site.

Anthracyclines probably represent the class of anticancer agents that has been most widely used for the development of prodrugs. This overview gives an update of the various low- and high-molecular weight prodrugs of anthracyclines, e.g. with antibodies, peptides, carbohydrates, serum proteins or synthetic polymers, that have been developed over the past 20 years and that exemplify the salient features of a respective drug delivery system. A detailed description will be dedicated to anthracycline prodrugs that have reached an advanced stage of preclinical testing or that have entered clinical trials.

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Keywords: Anticancer prodrugs; active and passive targeting; anthracyclines; cancer chemotherapy; doxorubicin; drug targeting

Document Type: Research Article

Affiliations: Felix Kratz, Head of Macromolecular Prodrugs, Tumor Biology Center, Breisacher Strasse 117, D-79106 Freiburg, Germany.

Publication date: 01 March 2006

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