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
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
-
Potential Therapeutic Advantages of Doxorubicin when Activated by Formaldehyde to Function as a DNA Adduct-Forming Agent
Current Topics in Medicinal Chemistry RNAi-based Gene Therapy for Dominant Limb Girdle Muscular Dystrophies
Current Gene Therapy Challenges and Opportunities from Basic Cancer Biology for Nanomedicine for Targeted Drug Delivery
Current Cancer Drug Targets Is Nephrogenic Systemic Fibrosis a Disease of Fibrocytes?
Current Rheumatology Reviews Heat Shock Proteins - Two Sides of a Coin
Current Cardiology Reviews Mitochondria as a Target for Exercise-Induced Cardioprotection
Current Drug Targets A Comparative Summary on Antioxidant-like Actions of Timolol with Other Antioxidants in Diabetic Cardiomyopathy
Current Drug Delivery Pharmacological Characteristics and Clinical Applications of K201
Current Clinical Pharmacology Application of G-CSF in Congestive Heart Failure Treatment
Current Cardiology Reviews Current Nervous System Related Drug Targets for the Treatment of Amyotrophic Lateral Sclerosis
Current Pharmaceutical Design Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes
Cardiovascular & Hematological Agents in Medicinal Chemistry How Cardiomyocytes Make the Heart Old
Current Pharmaceutical Biotechnology Cellular Membranes and Lipid-Binding Domains as Attractive Targets for Drug Development
Current Drug Targets Editorial: Look for Changes in 2016
Current Molecular Medicine Therapeutic Targeting of Endothelial Dysfunction in Chronic Diabetic Complications
Recent Patents on Cardiovascular Drug Discovery Biological Therapies: Effects of Proinflammatory Pathways and their Inhibition on the Myocardium of Rheumatoid Athritis Patients
Current Medicinal Chemistry Drug Uptake Systems in Liver and Kidney
Current Drug Metabolism A Comprehensive Review on Ethnomedicinal, Pharmacological and Phytochemical Basis of Anticancer Medicinal Plants of Pakistan
Current Cancer Drug Targets New Therapies to Modulate Post-Infarction Inflammatory Alterations in the Myocardium: State of the Art and Forthcoming Applications
Current Radiopharmaceuticals N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP): Potential target molecule in research of heart, kidney and brain
Current Pharmaceutical Design