Abstract
Topotecan and irinotecan (CPT-11) are both anticancer agents active in the inhibition of topoisomerase I, an enzyme involved in DNA replication and RNA transcription. During the last decades, an immense amount of research into this class of anticancer agents has been conducted, the positive results of which led to the clinical use of topotecan and CPT-11 in ovarian cancer and colorectal cancer, respectively. Here, we review the currently most important pharmacologic aspects of these drugs, including their mechanisms of action, metabolism, activity- and toxicity-profiles and mechanisms of resistance, to provide a global insight into their pharmacology. We also discuss the effects of combinations with other anticancer agents, which have been tested for synergistic antitumor effects. Pharmacokinetic and pharmacodynamic biomodulation, to enhance the bioavailability of the active anticancer agent or to reduce drug related toxicities have currently reached clinical application. As pharmacogenetics enters the clinical stage, this will lead to more “fine-tuning” in anticancer treatment (for instance by individualized dosing). The clarification of the mechanisms of action and resistance of topotecan and CPT-11 should enable us to understand their pharmacological behavior even better and might lead to the development of more potent camptothecinderivatives in the future.
Keywords: irinotecan, cpt-11, topotecan, topoisomerase I inhibitor, ovarian cancer, edorectal cancer, camptothecin
Current Cancer Drug Targets
Title: Pharmacology of Topoisomerase I Inhibitors Irinotecan (CPT-11) and Topotecan
Volume: 2 Issue: 2
Author(s): Ron H.J. Mathijssen, Walter J. Loos, Jaap Verweij and Alex Sparreboom
Affiliation:
Keywords: irinotecan, cpt-11, topotecan, topoisomerase I inhibitor, ovarian cancer, edorectal cancer, camptothecin
Abstract: Topotecan and irinotecan (CPT-11) are both anticancer agents active in the inhibition of topoisomerase I, an enzyme involved in DNA replication and RNA transcription. During the last decades, an immense amount of research into this class of anticancer agents has been conducted, the positive results of which led to the clinical use of topotecan and CPT-11 in ovarian cancer and colorectal cancer, respectively. Here, we review the currently most important pharmacologic aspects of these drugs, including their mechanisms of action, metabolism, activity- and toxicity-profiles and mechanisms of resistance, to provide a global insight into their pharmacology. We also discuss the effects of combinations with other anticancer agents, which have been tested for synergistic antitumor effects. Pharmacokinetic and pharmacodynamic biomodulation, to enhance the bioavailability of the active anticancer agent or to reduce drug related toxicities have currently reached clinical application. As pharmacogenetics enters the clinical stage, this will lead to more “fine-tuning” in anticancer treatment (for instance by individualized dosing). The clarification of the mechanisms of action and resistance of topotecan and CPT-11 should enable us to understand their pharmacological behavior even better and might lead to the development of more potent camptothecinderivatives in the future.
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Cite this article as:
Mathijssen H.J. Ron, Loos J. Walter, Verweij Jaap and Sparreboom Alex, Pharmacology of Topoisomerase I Inhibitors Irinotecan (CPT-11) and Topotecan, Current Cancer Drug Targets 2002; 2 (2) . https://dx.doi.org/10.2174/1568009023333890
DOI https://dx.doi.org/10.2174/1568009023333890 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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