ArticleCell stem cell2021
RARG variant predictive of doxorubicin-induced cardiotoxicity identifies a cardioprotective therapy.
Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 73 citations in OpenAlex.
- Childhood cancer and future cardiometabolic health.npj metabolic health and disease · 2026Review
- Genetic and Molecular Determinants of Cancer Therapy-Related Cardiovascular Toxicity.Cardiovascular toxicology · 2026Review
- Weekend-free and robotics-compatible protocols for high-throughput human-induced pluripotent stem cell maintenance, amplification, and differentiation.Stem cells translational medicine · 2026Article
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- Physiologically relevant 3D CRISPR screening enhances mechanistic insight into chemical toxicity compared to 2D screening.Toxicology · 2026Article
- CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes.G3 (Bethesda, Md.) · 2026Article
- Functional Genomics Illuminates Mechanisms of Anthracycline Cardiotoxicity.JACC. CardioOncology · 2026Article
- CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity.JACC. CardioOncology · 2026Article
- Caught in the crossfire: cardiac complications of cancer therapy.The Journal of clinical investigation · 2026Review
- predicTox: an integrated database of clinical risk frequencies and human gene expression signatures for cardiotoxic drugs.Database : the journal of biological databases and curation · 2026Article
- Cardiotoxicity associated with anticancer therapies for gynecological tumors.Frontiers in cardiovascular medicine · 2026Review
- Physiologically Relevant 3D CRISPR Screening Enhances Mechanistic Insight into Chemical Toxicity Compared to 2D Screening.bioRxiv : the preprint server for biology · 2025Article
- Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.Cell reports. Medicine · 2025Review
- Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.European journal of heart failure · 2025Review
- Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants.International journal of molecular sciences · 2025Review
- SNP's use as a potential chemotoxicity stratification tool in breast cancer: from bench to clinic.Functional & integrative genomics · 2025Review
- CDC20 protects the heart from doxorubicin-induced cardiotoxicity by modulating CCDC69 degradation.Cellular & molecular biology letters · 2025Article
- Mitochondrial Amount Determines Doxorubicin-Induced Cardiotoxicity in Cardiomyocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Applications of Single-Cell Omics Technologies for Induced Pluripotent Stem Cell-Based Cardiovascular Research.International journal of stem cells · 2025Review
- Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy.Nature reviews. Cancer · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Doxorubicin is an anthracycline chemotherapy agent effective in treating a wide range of malignancies, but its use is limited by dose-dependent cardiotoxicity. A recent genome-wide association study identified a SNP (rs2229774) in retinoic acid receptor-γ (RARG) as statistically associated with increased risk of anthracycline-induced cardiotoxicity. Here, we show that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with rs2229774 and who suffered doxorubicin-induced cardiotoxicity (DIC) are more sensitive to doxorubicin. We determine that the mechanism of this RARG variant effect is mediated via suppression of topoisomerase 2β (TOP2B) expression and activation of the cardioprotective extracellular regulated kinase (ERK) pathway. We use patient-specific hiPSC-CMs as a drug discovery platform, determining that the RARG agonist CD1530 attenuates DIC, and we confirm this cardioprotective effect in an established in vivo mouse model of DIC. This study provides a rationale for clinical prechemotherapy genetic screening for rs2229774 and a foundation for the clinical use of RARG agonist treatment to protect cancer patients from DIC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.