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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Nutriproteomics – Linking Proteomics Variation with Personalized Nutrition
Current Pharmacogenomics and Personalized Medicine Oncogenic Signaling Pathways Activated by RON Receptor Tyrosine Kinase
Current Cancer Drug Targets Cadmium and Its Epigenetic Effects
Current Medicinal Chemistry Nuclear Factor-κB: A Holy Grail in Cancer Prevention and Therapy
Current Signal Transduction Therapy Repurposing Drugs for Cancer Prevention
Current Topics in Medicinal Chemistry Aspirin as a Chemoprevention Agent for Colorectal Cancer
Current Drug Metabolism uPAR as Anti-Cancer Target: Evaluation of Biomarker Potential, Histological Localization, and Antibody-Based Therapy
Current Drug Targets PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development
Current Drug Targets Current Drug Design of Anti-HIV Agents Through the Inhibition of C-C Chemokine Receptor Type 5
Current Computer-Aided Drug Design Perspectives of Protein Kinase C (PKC) Inhibitors as Anti-Cancer Agents
Mini-Reviews in Medicinal Chemistry Calpain-Associated Proteolytic Regulation of the Stromal Microenvironment in Cancer
Current Pharmaceutical Design Metabolic Homeostasis and Colonic Health: the Critical Role of Short Chain Fatty Acids
Current Nutrition & Food Science Multimodality Imaging of CXCR4 in Cancer: Current Status towards Clinical Translation
Current Molecular Medicine Recent Patents on Alphavirus Protein Expression and Vector Production
Recent Patents on Biotechnology Agents Targeting Ras Signaling Pathway
Current Pharmaceutical Design Endoplasmic Reticulum Stress, Calcium Dysregulation and Altered Protein Translation: Intersection of Processes That Contribute to Cancer Cachexia Induced Skeletal Muscle Wasting
Current Drug Targets Targeting Karyotypic Complexity and Chromosomal Instability of Cancer Cells
Current Drug Targets Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones
Current Cancer Drug Targets Anti-cancer Effects of Metformin: Recent Evidences for its Role in Prevention and Treatment of Cancer
Current Drug Metabolism A Novel Method for Microsatellite Instability Detection by Liquid Biopsy Based on Next-generation Sequencing
Current Bioinformatics