![conference banner](/images/conference-banner.jpeg)
Abstract
Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity. Inhibition of the TopoIIb isoform has been implicated in this cytotoxicity. Response to TopoII active agents is determined by several factors, but cell cycle checkpoints play a large role in sensitivity and resistance. The G2/M phase checkpoints are of particular importance in considering the effectiveness of these drugs and are reviewed in this article. Functionality of the ATM dependent decatenation checkpoint may represent a new avenue for selective cancer therapy. Here we review the function of TopoII, the anti-cancer mechanisms and limitations of current catalytic inhibitors and poisons, and their influence on cell cycle checkpoints. We will also assess potential new mechanisms for targeting this enzyme to limit normal tissue toxicity, and how the cell cycle checkpoint triggered by these drugs may provide an alternative and possibly better target for novel therapies.
Keywords: Topoisomerase II, cell cycle checkpoints, genome integrity, cytotoxicity, G2/M phase checkpoints, TopoII poison.
Current Medicinal Chemistry
Title:Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints
Volume: 24 Issue: 15
Author(s): Nicholas D`Arcy and Brian Gabrielli*
Affiliation:
- Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane 4102 Queensland,Australia
Keywords: Topoisomerase II, cell cycle checkpoints, genome integrity, cytotoxicity, G2/M phase checkpoints, TopoII poison.
Abstract: Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity. Inhibition of the TopoIIb isoform has been implicated in this cytotoxicity. Response to TopoII active agents is determined by several factors, but cell cycle checkpoints play a large role in sensitivity and resistance. The G2/M phase checkpoints are of particular importance in considering the effectiveness of these drugs and are reviewed in this article. Functionality of the ATM dependent decatenation checkpoint may represent a new avenue for selective cancer therapy. Here we review the function of TopoII, the anti-cancer mechanisms and limitations of current catalytic inhibitors and poisons, and their influence on cell cycle checkpoints. We will also assess potential new mechanisms for targeting this enzyme to limit normal tissue toxicity, and how the cell cycle checkpoint triggered by these drugs may provide an alternative and possibly better target for novel therapies.
Export Options
About this article
Cite this article as:
D`Arcy Nicholas and Gabrielli Brian*, Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints, Current Medicinal Chemistry 2017; 24 (15) . https://dx.doi.org/10.2174/0929867323666161205122613
DOI https://dx.doi.org/10.2174/0929867323666161205122613 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
- Announcements
Related Articles
-
Baseline Levels of Interleukine-6, Tumor-Necrosis Factor-Alpha and C-Reactive Protein in Treatment Naive Human Immunodeficiency Virus Infected Patients-A Study from a Tertiary-Care Hospital in Eastern India
Current Biomarkers (Discontinued) Apigenin, A Plant Flavone Playing Noble Roles in Cancer Prevention Via Modulation of Key Cell Signaling Networks
Recent Patents on Anti-Cancer Drug Discovery Is there a Possible Single Mediator in Modulating Neuroendocrine–thymus Interaction in Ageing?
Current Aging Science Life and Death of Leukemic Cells Under Bcr-Abl Signaling Control
Current Cancer Therapy Reviews Significance of Prion and Prion-Like Proteins in Cancer Development, Progression and Multi-Drug Resistance
Current Cancer Drug Targets Platelet Activity in the Pathophysiology of Inflammatory Bowel Diseases
Current Drug Targets Posttranslational Regulation of O6-Methylguanine-DNA Methyltransferase (MGMT) and New Opportunities for Treatment of Brain Cancers
Mini-Reviews in Medicinal Chemistry Extracellular Production of the Oncolytic Enzyme, L-Asparaginase, by Newly Isolated Streptomyces sp. Strain NEAE-95 as Potential Microbial Cell Factories: Optimization of Culture Conditions Using Response Surface Methodology
Current Pharmaceutical Biotechnology Retinoic Acid Signaling in P19 Stem Cell Differentiation
Anti-Cancer Agents in Medicinal Chemistry Targeted Cancer Stem Cell Therapeutics: An Update
Current Topics in Medicinal Chemistry Thrombotic Microangiopathy and Occult Neoplasia
Cardiovascular & Hematological Disorders-Drug Targets Monoclonal Antibodies in Clinical Oncology
Anti-Cancer Agents in Medicinal Chemistry Tumor Stem Cell Niches: A New Functional Framework for the Action of Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery Neurodegenerative Disease: A Perspective on Cell-Based Therapy in the New Era of Cell-Free Nano-Therapy
Current Pharmaceutical Design Endoradiotherapy with Peptides - Status and Future Development
Current Medicinal Chemistry Quinoxalines Potential to Target Pathologies
Current Medicinal Chemistry A Role for the Inflammatory Mediators Cox-2 and Metalloproteinases in Cancer Stemness
Anti-Cancer Agents in Medicinal Chemistry Azathioprine in Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry Paving Roads for New Drugs in Oncology
Recent Patents on Anti-Cancer Drug Discovery Regulation of the DNA Damage Response to DSBs by Post-Translational Modifications
Current Genomics