Pediatric Anthracycline-Induced Cardiotoxicity: Mechanisms, Pharmacogenomics, and Pluripotent Stem-Cell Modeling

Clin Pharmacol Ther. 2019 Mar;105(3):614-624. doi: 10.1002/cpt.1311. Epub 2019 Jan 11.

Abstract

Anthracycline-induced cardiotoxicity (ACT) is a severe adverse drug reaction for a subset of children treated with anthracyclines as part of chemotherapy protocols. The identification of genetic markers associated with increased ACT susceptibility has clinical significance toward improving patient care and our understanding of the molecular mechanisms involved in ACT. Human-induced pluripotent stem cell-derived cardiomyocytes represent a novel approach to determine the pharmacogenomics of ACT and guide the development of genetic screening tests.

Publication types

  • Review

MeSH terms

  • Anthracyclines / adverse effects*
  • Anthracyclines / chemistry
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / chemistry
  • Cardiotoxins / adverse effects*
  • Cardiotoxins / chemistry
  • Child
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / metabolism
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Pharmacogenetics / trends*

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Cardiotoxins