Abstract
Anthracyclines are among the most effective anticancer drugs ever developed. Unfortunately, their clinical use is severely limited by the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure, usually refractory to conventional therapy. The pathophysiology of anthracycline-induced cardiomyopathy remains controversial and incompletely understood. The current thinking is that anthracyclines are toxic per se but gain further cardiotoxicity after one-electron reduction with ROS overproduction or two-electron reduction with conversion to C-13 alcohol metabolites. ROS overproduction can probably be held responsible for anthracycline acute cardiotoxicity, but not for all the aspects of progressive cardiomyopathy. Intramyocardial formation of secondary alcohol metabolites might play a key role in promoting the progression of cardiotoxicity toward end-stage cardiomyopathy and congestive heart failure. In this review we also discuss recent developments in: a) the molecular mechanisms underlying anthracycline-induced cardiotoxicity; b) the role of cytosolic NADPH-dependent reductases in anthracycline metabolism; c) the influence of genetic polymorphisms on cardiotoxicity outcome; d) the perspectives on the most promising strategies for limiting or preventing anthracycline-induced cardiotoxicity, focusing on controversial aspects and on recent data regarding analogues of the natural compounds, tumor-targeted formulations and cardioprotective agents.
Keywords: Anthracycline, secondary alcohol metabolites, cardiotoxicity, aldo-keto reductases, carbonyl reductases, genetic polymorphisms
Current Medicinal Chemistry
Title: New Developments in Anthracycline-Induced Cardiotoxicity
Volume: 16 Issue: 13
Author(s): A. Mordente, E. Meucci, A. Silvestrini, G. E. Martorana and B. Giardina
Affiliation:
Keywords: Anthracycline, secondary alcohol metabolites, cardiotoxicity, aldo-keto reductases, carbonyl reductases, genetic polymorphisms
Abstract: Anthracyclines are among the most effective anticancer drugs ever developed. Unfortunately, their clinical use is severely limited by the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure, usually refractory to conventional therapy. The pathophysiology of anthracycline-induced cardiomyopathy remains controversial and incompletely understood. The current thinking is that anthracyclines are toxic per se but gain further cardiotoxicity after one-electron reduction with ROS overproduction or two-electron reduction with conversion to C-13 alcohol metabolites. ROS overproduction can probably be held responsible for anthracycline acute cardiotoxicity, but not for all the aspects of progressive cardiomyopathy. Intramyocardial formation of secondary alcohol metabolites might play a key role in promoting the progression of cardiotoxicity toward end-stage cardiomyopathy and congestive heart failure. In this review we also discuss recent developments in: a) the molecular mechanisms underlying anthracycline-induced cardiotoxicity; b) the role of cytosolic NADPH-dependent reductases in anthracycline metabolism; c) the influence of genetic polymorphisms on cardiotoxicity outcome; d) the perspectives on the most promising strategies for limiting or preventing anthracycline-induced cardiotoxicity, focusing on controversial aspects and on recent data regarding analogues of the natural compounds, tumor-targeted formulations and cardioprotective agents.
Export Options
About this article
Cite this article as:
Mordente A., Meucci E., Silvestrini A., Martorana E. G. and Giardina B., New Developments in Anthracycline-Induced Cardiotoxicity, Current Medicinal Chemistry 2009; 16 (13) . https://dx.doi.org/10.2174/092986709788186228
DOI https://dx.doi.org/10.2174/092986709788186228 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Statins and Vulnerable Plaque
Current Pharmaceutical Design Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Diabetic Retinopathy: Mechanistic Insights into High Glucose-Induced Retinal Cell Death
Current Clinical Pharmacology Peripartum Cardiomyopathy: An Intensivist's Perspective
Current Women`s Health Reviews Heart Failure in the Middle East
Current Cardiology Reviews Current Biology of MTP: Implications for Selective Inhibition
Current Topics in Medicinal Chemistry Epidermolysis Bullosa: Pediatric Perspectives
Current Pediatric Reviews Diabetes and Chronic Heart Failure: From Diabetic Cardiomyopathy to Therapeutic Approach
Endocrine, Metabolic & Immune Disorders - Drug Targets Cardiac Multidetector Computed Tomography: Basic Physics of Image Acquisition and Clinical Applications
Current Cardiology Reviews Vascular Oxidative Stress: A Key Factor in the Development of Hypertension Associated with Ethanol Consumption
Current Hypertension Reviews Restoration of Chemoresistance Mechanism by Novel Drug Therapies in Breast Cancer Cell Lines
Current Drug Therapy Distribution of Left Ventricular Thrombus among Patients with Significantly Impaired Systolic Function
New Emirates Medical Journal Multiple Drug Resistance Associated with Function of ABC-Transporters in Diabetes Mellitus: Molecular Mechanism and Clinical Relevance
Infectious Disorders - Drug Targets The Meaning of Different Forms of Structural Myocardial Injury, Immune Response and Timing of Infarct Necrosis and Cardiac Repair
Current Vascular Pharmacology Pharmacological and Non Pharmacological Strategies in the Management of Coronary Artery Disease and Chronic Kidney Disease
Current Cardiology Reviews Cellular Membranes and Lipid-Binding Domains as Attractive Targets for Drug Development
Current Drug Targets Human Immunodeficiency Virus (HIV) and Stroke: Targets for Intervention
Infectious Disorders - Drug Targets Endothelins Role in the Control of the Acute Phase of Trypanosoma cruzi Infection
Mini-Reviews in Medicinal Chemistry Diabetes and Vascular Disease: Is It All About Glycemia?
Current Pharmaceutical Design Flavonoids as Potential Therapeutic Agents for the Management of Diabetic Neuropathy
Current Pharmaceutical Design Role of Secondary Alcohol Metabolites in Anthracycline Cardiotoxicity: from Hypotheses to New Drugs
Drug Design Reviews - Online (Discontinued)