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Cardioprotection in Drug-Induced Cardiotoxicity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 August 2025) | Viewed by 2708

Special Issue Editor


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Guest Editor
Department of Pharmacology & Therapeutics, School of Medicine, College of Medicine and Health, University College Cork, T12 K8AF Cork, Ireland
Interests: cardioprotection; Cardiooncology; heart failure; myocardial infarction; ischemia-reperfusuin; phospholipid metabolism

Special Issue Information

Dear Colleagues,

More people are surviving cancer due to improved screening programmes and treatment options; however, many of these survivors go on to develop cardiac problems because of the drugs used to treat their cancer. This increased survival has highlighted the negative impact of some anticancer drugs on the heart. For example, Doxorubicin (Adriamycin), Fluoropyrimidines, and immune checkpoint inhibitors are effective drugs in the treatment of cancer, but they have been linked to significant cardiotoxic effects which affect morbidity and mortality. For many of these cancers, there is no equally effective alternative drug. Thus, an option is to cotreat these patients with an agent that minimises cardiotoxicity. However, very few such agents exist.

This Special Issue seeks to explore novel cardioprotective targets for drug-induced cardiotoxicity as well as innovative strategies for identifying and investigating cardioprotective agents in drug-induced cardiotoxicity. A better understanding of molecular mechanisms together with innovative solutions will help to shape the future of pharmacotherapy. This Special Issue welcomes review articles and primary research on the following (or related) topics:

  1. Novel molecular drug targets for protecting the heart in drug-induced cardiotoxicity (including, but not limited to, RNA therapeutics, epigenetic targets, gut–microbiome interactions, etc.);
  2. New approaches to existing molecular targets used to protect the heart in drug-induced cardiotoxicity;
  3. Novel methods and models for the identification of molecules and pathways that can protect the heart in drug-induced cardiotoxicity (including, but not limited to, computational methods, cell models, novel molecular methods, pharmacogenomics, etc.).

Dr. Roisin Kelly-Laubscher
Guest Editor

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Keywords

  • cardioprotection
  • cardiotoxicity
  • anthracycline
  • cardiac dysfunction
  • heart failure

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Published Papers (3 papers)

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Research

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18 pages, 519 KB  
Article
Drugs Metabolism-Related Genes Variants Impact on Anthracycline-Based Chemotherapy Induced Subclinical Cardiotoxicity in Breast Cancer Patients
by Domas Vaitiekus, Gintare Muckiene, Dovydas Verikas, Audrone Vaitiekiene, Skaiste Astasauskaite, Rolandas Gerbutavicius, Agne Bartnykaite, Rasa Ugenskienė, Renaldas Jurkevičius and Elona Juozaitytė
Int. J. Mol. Sci. 2025, 26(9), 4051; https://doi.org/10.3390/ijms26094051 - 25 Apr 2025
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Abstract
Breast cancer is the most common cancer in women worldwide. Anthracyclines (doxorubicin, epirubicin, daunorubicin, idarubicin) are among the most used drugs for the treatment of breast cancer. Unfortunately, anthracyclines cause cardiotoxicity, which is a limiting factor for its use, and the lifetime cumulative [...] Read more.
Breast cancer is the most common cancer in women worldwide. Anthracyclines (doxorubicin, epirubicin, daunorubicin, idarubicin) are among the most used drugs for the treatment of breast cancer. Unfortunately, anthracyclines cause cardiotoxicity, which is a limiting factor for its use, and the lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. In our study, we focused on acute and subacute heart damage. One of the main factors is a genetic predisposition, which determines individual susceptibility to anthracycline cardiotoxicity. The main idea of this study was, for the first time, to evaluate drug metabolism-related genes as a risk factor for developing cardiovascular toxicity in breast cancer patients. The main objective of our study was to identify the impact of drug metabolism-related gene SNPs on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. The data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in an outpatient clinic were analyzed, and SNP RT-PCR tests were performed. The drug metabolism-related gene variants SULT2B1 rs10426377, UGT1A6 rs17863783, CBR1 rs9024, CBR3 rs1056892, NCF4 rs1883112, and CYBA rs1049255 did not reach a statistically important impact on ABCC in multivariate logistic regression analysis. However, we identified that NCF4 rs1883112 had a risk reduction tendency for ABCC (OR = 0.49, 95% CI 0.27–0.87, p = 0.015). Our findings suggest that some SNPs, such as NCF4 rs1883112, may be associated with a reduced risk of cardiotoxicity, while no variants in this study showed a statistically significant increased risk. Even though, NCF4 rs1883112 showed a risk reduction tendency, suggesting the potential for personalized risk stratification. We can conclude that multiple genes are involved in ABCC, with different impacts, and it is unlikely that there is a single driver gene in ABCC pathogenesis. Full article
(This article belongs to the Special Issue Cardioprotection in Drug-Induced Cardiotoxicity)
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Review

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20 pages, 696 KB  
Review
Ubiquitin E3 Ligases and p53 in Doxorubicin-Induced Cardiotoxicity
by Shingo Tachibana, Yoichiro Otaki, Jun Goto, Tetsu Watanabe and Masafumi Watanabe
Int. J. Mol. Sci. 2025, 26(21), 10252; https://doi.org/10.3390/ijms262110252 - 22 Oct 2025
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Abstract
Doxorubicin (Dox) is a widely used anti-cancer drug. It has proven efficacy against various cancers, although the clinical application of Dox has been limited due to dose-dependent, irreversible, and fatal Dox-induced cardiotoxicity (DIC). The mechanism of DIC remains unclear. p53 plays a key [...] Read more.
Doxorubicin (Dox) is a widely used anti-cancer drug. It has proven efficacy against various cancers, although the clinical application of Dox has been limited due to dose-dependent, irreversible, and fatal Dox-induced cardiotoxicity (DIC). The mechanism of DIC remains unclear. p53 plays a key role in DIC via cardiomyocyte loss due to cell death and oxidative stress. Its expression is strictly controlled by post-translational modifications, and its suppression in cardiomyocytes reportedly ameliorates DIC. The ubiquitin system regulates biological processes that are fundamental to the development of cardiovascular diseases. The dysregulation of several ubiquitin E3 ligases is reportedly associated with DIC development through the upregulation of p53. Ubiquitin E3 ligases are classified into four groups; all classes of E3 ligases are involved in p53 degradation. In this review, we focus on recently emerging topics regarding the role of E3 ligases in the regulation of p53 degradation. We also provide an overview of the functional roles of E3 ligases in DIC. Recent reports have identified cardioprotective agents for DIC through ubiquitin E3 ligase-mediated p53 suppression. Here, we present some findings regarding the current development of cardioprotective agents for DIC. These agents may serve as a novel therapeutic target for the treatment of DIC. Full article
(This article belongs to the Special Issue Cardioprotection in Drug-Induced Cardiotoxicity)
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25 pages, 898 KB  
Review
Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection
by Marija Kosić, Vladislav Pajović, Mirjana Jovanović and Nina Japundžić-Žigon
Int. J. Mol. Sci. 2025, 26(20), 10130; https://doi.org/10.3390/ijms262010130 - 17 Oct 2025
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Abstract
Doxorubicin (DOX) is an effective drug for the treatment of solid tumors and hematological malignancies in both children and adults. The most serious side effect is doxorubicin-induced cardiotoxicity (DIC), which can lead to cardiomyopathy and irreversible and highly fatal cardiac decompensation. The precise [...] Read more.
Doxorubicin (DOX) is an effective drug for the treatment of solid tumors and hematological malignancies in both children and adults. The most serious side effect is doxorubicin-induced cardiotoxicity (DIC), which can lead to cardiomyopathy and irreversible and highly fatal cardiac decompensation. The precise mechanisms underlying DIC are not fully understood, and currently, no fully effective preventive or therapeutic strategies exist. Drug repositioning has emerged as a promising approach to mitigate DIC, leveraging existing safety profiles while potentially reducing the time and cost of clinical translation. In this review, we summarize current evidence on drug repurposing for DIC, with a particular focus on the antidepressant paroxetine, which shows potential cardioprotective effects beyond its established role as a selective serotonin reuptake inhibitor (SSRI). Full article
(This article belongs to the Special Issue Cardioprotection in Drug-Induced Cardiotoxicity)
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