Anthracycline Toxicity: Light at the End of the Tunnel?

Romina B. Cejas, Kateryna Petrykey, Yadav Sapkota, Paul W. Burridge

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Anthracycline-induced cardiotoxicity (AIC) is a serious and common side effect of anthracycline therapy. Identification of genes and genetic variants associated with AIC risk has clinical potential as a cardiotoxicity predictive tool and to allow the development of personalized therapies. In this review, we provide an overview of the function of known AIC genes identified by association studies and categorize them based on their mechanistic implication in AIC. We also discuss the importance of functional validation of AIC-associated variants in human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) to advance the implementation of genetic predictive biomarkers. Finally, we review how patient-specific hiPSC-CMs can be used to identify novel patient-relevant functional targets and for the discovery of cardioprotectant drugs to prevent AIC. Implementation of functional validation and use of hiPSC-CMs for drug discovery will identify the next generation of highly effective and personalized cardioprotectants and accelerate the inclusion of approved AIC biomarkers into clinical practice.

Original languageEnglish (US)
Pages (from-to)115-134
Number of pages20
JournalAnnual Review of Pharmacology and Toxicology
Volume64
DOIs
StatePublished - Jan 23 2024

Keywords

  • biomarkers
  • cardioprotectants
  • cardiotoxicity
  • chemotherapy
  • doxorubicin
  • hiPSC-CMs

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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