Abstract
Topoisomerases are ubiquitous enzymes involved in maintaining genomic stability of the cell by regulating the over- or underwinding of DNA strands. Besides their customary functions, topoisomerases are important cellular targets of widely used anticancer drugs. In particular, topoisomerase IIα (Top2α) has been postulated as the primary molecular target of anthracycline’s anticancer activity, whereas topoisomerase IIβ (Top2β), the only Top2 present in heart tissue, seems to be involved in the development of anthracycline-induced cardiotoxicity. Noteworthy, cardiotoxicity is the most frequent adverse effect of both conventional and modern anticancer targeted therapy, representing the leading noncancer-related cause of morbidity and mortality in long-term survivors. The molecular mechanisms of anthracyclineinduced cardiotoxicity have been investigated for decades and, despite the numerous mechanistic hypotheses put forward, its aetiology and pathogenesis still remain controversial.
This review is aimed at focusing on the double edge sword of topoisomerase-anthracycline interaction, and, in particular, on the potential role of topoisomerases in anthracyclines anticancer activity as well as in the pathogenesis of anthracycline-induced cardiotoxicity.Keywords: Anthracycline, cancer chemotherapy, cardio-oncology, cardiotoxicity, catalytic inhibitors, DNA topoisomerases, topoisomerase poisons.
Current Medicinal Chemistry
Title:Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity
Volume: 24 Issue: 15
Author(s): Alvaro Mordente*, Elisabetta Meucci, Giuseppe Ettore Martorana, Daniela Tavian and Andrea Silvestrini*
Affiliation:
- Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome,Italy
- Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome,Italy
Keywords: Anthracycline, cancer chemotherapy, cardio-oncology, cardiotoxicity, catalytic inhibitors, DNA topoisomerases, topoisomerase poisons.
Abstract: Topoisomerases are ubiquitous enzymes involved in maintaining genomic stability of the cell by regulating the over- or underwinding of DNA strands. Besides their customary functions, topoisomerases are important cellular targets of widely used anticancer drugs. In particular, topoisomerase IIα (Top2α) has been postulated as the primary molecular target of anthracycline’s anticancer activity, whereas topoisomerase IIβ (Top2β), the only Top2 present in heart tissue, seems to be involved in the development of anthracycline-induced cardiotoxicity. Noteworthy, cardiotoxicity is the most frequent adverse effect of both conventional and modern anticancer targeted therapy, representing the leading noncancer-related cause of morbidity and mortality in long-term survivors. The molecular mechanisms of anthracyclineinduced cardiotoxicity have been investigated for decades and, despite the numerous mechanistic hypotheses put forward, its aetiology and pathogenesis still remain controversial.
This review is aimed at focusing on the double edge sword of topoisomerase-anthracycline interaction, and, in particular, on the potential role of topoisomerases in anthracyclines anticancer activity as well as in the pathogenesis of anthracycline-induced cardiotoxicity.Export Options
About this article
Cite this article as:
Mordente Alvaro*, Meucci Elisabetta, Martorana Ettore Giuseppe, Tavian Daniela and Silvestrini Andrea*, Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity, Current Medicinal Chemistry 2017; 24 (15) . https://dx.doi.org/10.2174/0929867323666161214120355
DOI https://dx.doi.org/10.2174/0929867323666161214120355 |
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
- 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
-
Crude Venom from Nematocysts of the Jellyfish Pelagia noctiluca as a Tool to Study Cell Physiology
Central Nervous System Agents in Medicinal Chemistry Role of Autophagy in Alzheimer’s Disease
Current Enzyme Inhibition Statins and Oxidative Stress in the Cardiovascular System
Current Pharmaceutical Design Eisenmenger Syndrome: Recent Advances in Pharmacotherapy
Cardiovascular & Hematological Agents in Medicinal Chemistry Co-formulation of P-glycoprotein Substrate and Inhibitor in Nanocarriers: An Emerging Strategy for Cancer Chemotherapy
Current Cancer Drug Targets MicroRNAs in Organogenesis and Disease
Current Molecular Medicine Combating Obesity by Targeting Nuclear Receptors
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Patent Selections
Recent Patents on Cardiovascular Drug Discovery Actions of Relaxin on Non-Reproductive Tissues
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Molecular Signals Elicited by GPCR Agonists in Hypertension, Cardiovascular Remodeling: Are MMPs and ADAMs Elusive Therapeutic Targets?
Current Hypertension Reviews A Review on the Sex Differences in Organ and System Pathology with Alcohol Drinking
Current Drug Abuse Reviews Cross-Talk Between Adipose Tissue Health, Myocardial Metabolism and Vascular Function: The Adipose-Myocardial and Adipose-Vascular Axes
Current Pharmaceutical Design A Review on Hematopoietic Stem Cell Treatment for Epilepsy
CNS & Neurological Disorders - Drug Targets Update on the Adverse Effects of Clozapine: Focus on Myocarditis
Current Drug Safety Circulating Biomarkers of Collagen Metabolism and Prognosis of Heart Failure with Reduced or Mid-Range Ejection Fraction
Current Pharmaceutical Design The Therapeutic Potential of Hepatocyte Growth Factor for Myocardial Infarction and Heart Failure
Current Pharmaceutical Design Pulmonary Hypertension and Systemic Diseases
Current Drug Targets - Inflammation & Allergy Pharmacologic Therapy in Growth Hormone Disorders and the Heart
Current Medicinal Chemistry Cardiac Remodeling and Exercise Training in Hypertension
Current Hypertension Reviews Flavonoids as Potential Therapeutic Agents for the Management of Diabetic Neuropathy
Current Pharmaceutical Design