Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes

Nat Rev Drug Discov. 2011 Feb;10(2):111-26. doi: 10.1038/nrd3252.


Targeted therapeutics, particularly those that inhibit the activity of protein kinases that are mutated and/or overexpressed in cancer, have revolutionized the treatment of some cancers and improved survival rates in many others. Although these agents dominate drug development in cancer, significant toxicities, including cardiotoxicity, have emerged. In this Review, we examine the underlying mechanisms that result in on-target or off-target cardiotoxicities of small molecule kinase inhibitors. We also discuss how well the various preclinical safety models and strategies might predict clinical cardiotoxicity. It is hoped that a thorough understanding of the mechanisms underlying cardiotoxicity will lead to the development of safe, effective drugs and consequently, fewer costly surprises as agents progress through clinical trials.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiotoxins / adverse effects
  • Cardiotoxins / pharmacokinetics
  • Cardiotoxins / therapeutic use*
  • Clinical Trials as Topic / methods*
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome


  • Cardiotoxins
  • Protein Kinase Inhibitors