CommentariesA critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin
Section snippets
Proposed mechanisms of drug action
To evaluate the mechanisms of drug action that may be relevant to the clinical effectiveness of these agents, it is necessary to establish the actual drug concentrations that are achieved and/or sustained in patients undergoing treatment. At doses for bolus administration varying between 15 and 90 mg/m2, the maximal initial plasma concentration detected was approximately 5 μM 96, 97, while the lowest reported concentration was approximately 0.3 μM [98]; generally, initial plasma concentrations
Summary
In summary, it appears that the multiple mechanisms of action that have been ascribed to the anthracyclines may be related to the utilization of different drug concentrations under varied experimental conditions. When cells are exposed to drug concentrations in the submicromolar range, induction of cell differentiation (with prolonged exposure) and interference with DNA unwinding/DNA strand separation and DNA helicase may be evident. At drug concentrations that reflect the peak plasma
Acknowledgements
This work was supported by Grant CA55815 from the National Institutes of Health/National Cancer Institute and United States Army Medical Research and Material Command Award DAMD 17–96-1–6167. The author would like to acknowledge Dr. James Doroshow for providing a copy of his review and to thank Dr. Nicholas Bachur and Dr. Karen Magnet for critical reading of the manuscript and helpful suggestions for revision.
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