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- W2147809056 startingPage "1656" @default.
- W2147809056 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" @default.
- W2147809056 created "2016-06-24" @default.
- W2147809056 creator A5011644516 @default.
- W2147809056 creator A5015405335 @default.
- W2147809056 creator A5021881282 @default.
- W2147809056 creator A5069384526 @default.
- W2147809056 creator A5082093327 @default.
- W2147809056 date "2009-05-01" @default.
- W2147809056 modified "2023-10-17" @default.
- W2147809056 title "New Developments in Anthracycline-Induced Cardiotoxicity" @default.
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