New developments in anthracycline-induced cardiotoxicity

Curr Med Chem. 2009;16(13):1656-72. doi: 10.2174/092986709788186228.


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.

Publication types

  • Review

MeSH terms

  • Anthracyclines / toxicity*
  • Cytosol / metabolism
  • Heart / drug effects*
  • Humans
  • NADP / metabolism
  • Polymorphism, Genetic
  • Reactive Oxygen Species / metabolism


  • Anthracyclines
  • Reactive Oxygen Species
  • NADP