Physiological, pharmacological and toxicological considerations of drug-induced structural cardiac injury

Br J Pharmacol. 2015 Feb;172(4):957-74. doi: 10.1111/bph.12979. Epub 2015 Jan 12.

Abstract

The incidence of drug-induced structural cardiotoxicity, which may lead to heart failure, has been recognized in association with the use of anthracycline anti-cancer drugs for many years, but has also been shown to occur following treatment with the new generation of targeted anti-cancer agents that inhibit one or more receptor or non-receptor tyrosine kinases, serine/threonine kinases as well as several classes of non-oncology agents. A workshop organized by the Medical Research Council Centre for Drug Safety Science (University of Liverpool) on 5 September 2013 and attended by industry, academia and regulatory representatives, was designed to gain a better understanding of the gaps in the field of structural cardiotoxicity that can be addressed through collaborative efforts. Specific recommendations from the workshop for future collaborative activities included: greater efforts to identify predictive (i) preclinical; and (ii) clinical biomarkers of early cardiovascular injury; (iii) improved understanding of comparative physiology/pathophysiology and the clinical predictivity of current preclinical in vivo models; (iv) the identification and use of a set of cardiotoxic reference compounds for comparative profiling in improved animal and human cellular models; (v) more sharing of data (through publication/consortia arrangements) on target-related toxicities; (vi) strategies to develop cardio-protective agents; and (vii) closer interactions between preclinical scientists and clinicians to help ensure best translational efforts.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Cardiotoxicity / etiology*
  • Cardiotoxicity / metabolism
  • Cardiotoxicity / pathology
  • Cardiotoxicity / physiopathology
  • Cardiotoxins / adverse effects*
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / physiopathology
  • Humans

Substances

  • Antineoplastic Agents
  • Cardiotoxins