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Use of hiPSC to explicate genomic predisposition to anthracycline-induced cardiotoxicity

Tarek Magdy1,2, Paul W Burridge1,2

  • 1Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Pharmacogenomics
|January 15, 2021
PubMed

Insights

Researchers are exploring genetic factors influencing heart damage from anthracycline chemotherapy. Human stem cell-derived heart cells offer a new way to validate genetic variants linked to anthracycline-induced cardiotoxicity (AIC).

Area of Science:

  • Pharmacogenomics
  • Cardiology
  • Stem Cell Biology

Background:

  • Anthracyclines are potent anticancer drugs but can cause severe heart damage.
  • Anthracycline-induced cardiotoxicity (AIC) susceptibility varies among patients.
  • Over 60 genetic loci linked to AIC have been identified, but none are clinically validated biomarkers.

Purpose of the Study:

  • To provide an overview of genetic variants associated with AIC.
  • To highlight the potential of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in validating these variants.
  • To explain the genomic basis of patient predisposition to AIC.

Main Methods:

  • Review of existing pharmacogenomic studies on AIC.
  • Discussion of advancements in sequencing and genomic editing.
  • Application of hiPSC-CMs for functional validation of genetic variants.

Main Results:

  • Numerous genetic loci associated with AIC have been identified through pharmacogenomic studies.
  • hiPSC-CMs provide a human model for validating the functional impact of AIC-associated genetic variants.
  • This approach facilitates a deeper understanding of AIC's genomic underpinnings.

Conclusions:

  • Genetic factors significantly influence an individual's risk of AIC.
  • hiPSC-CMs represent a promising platform for validating AIC genetic biomarkers.
  • Further research using hiPSC-CMs could lead to personalized AIC risk assessment and prevention strategies.
Keywords:
cardiomyocytecardiotoxicitygenomic editinghuman-induced pluripotent stem cellspharmacogenomics

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