What is the clinical evidence from this study?

Study design: Other. Population: Doxorubicin-induced cardiotoxicity. Intervention: Doxorubicin vs. saline. Primary outcome: Differentially expressed genes and proteins.

What does this research mean for the field?

Doxorubicin causes upregulation of stress-responsive and apoptosis-related pathways, with elevated plasma SERPINA3 in breast cancer patients 24 hours post-treatment. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim is to investigate the mechanisms underlying doxorubicin-induced cardiotoxicity using a multi-omics approach.

February 2, 2026PharmaceuticalsOpen Access

Integrated Omics Approach to Delineate the Mechanisms of Doxorubicin-Induced Cardiotoxicity

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Key result

Doxorubicin upregulates stress and apoptosis pathways and elevates plasma SERPINA3 in breast cancer patients.

Why the study?

Doxorubicin is an effective chemotherapeutic agent, but its clinical utility is limited by cardiotoxicity.

Population

Five-week-old male mice and DOX-treated breast cancer patients

Comparison

Weekly DOX (4 mg/kg) vs saline injections for six weeks

Design

Preclinical multi-omics study with clinical biomarker validation

Follow-up

4 days and 6 weeks post-treatment

Authors

MDMohamed S. DabourUniversity of Minnesota IAIbrahim Y. AbdelgawadCross-Cutting Cardiology BSBushra SadafUniversity of Minnesota

Discussion

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Implication

SERPINA3 may flag early doxorubicin cardiotoxicity risk; leaves open biomarker utility pending prospective validation.

Key Points

The aim is to investigate the mechanisms underlying doxorubicin-induced cardiotoxicity using a multi-omics approach.
Utilized male mice receiving DOX or saline injections over six weeks.
Harvested heart tissues for RNA-seq and proteomics analysis four days post-treatment.
Validated differentially expressed genes and proteins using qPCR and Western blot.
Conducted gene set enrichment analysis to identify enriched pathways.
Compared temporal changes in gene and protein expression at different time points post-DOX.
RNA-seq identified upregulation of stress-responsive and circadian genes and downregulation of Apelin and Cd74.
Proteomics showed an increase in SERPINA3, thrombospondin-1, and epoxide hydrolase 1.
Plasma SERPINA3 levels were significantly higher in breast cancer patients post-DOX.
Increased expression of genes related to p53 signaling and apoptosis was observed in the heart tissue.
Dynamic changes were noted over time, with inflammation early and DNA repair processes dominant later.

Structured PICO

Population

Five-week-old male mice and DOX-treated breast cancer patients studied to investigate mechanisms of doxorubicin-induced cardiotoxicity.

Intervention

Weekly doxorubicin (4 mg/kg) injections for six weeks

Comparator

Saline injections

Outcome

Differentially expressed genes (DEGs) and proteins (DEPs) in heart tissues 4 days post-treatmentsurrogate

This integrated omics study delineates the molecular mechanisms of doxorubicin-induced cardiotoxicity, identifying SERPINA3 as a potential biomarker.

Cite This Study

Dabour et al. (2026) studied Doxorubicin-induced cardiotoxicity. Doxorubicin vs. saline was evaluated on Differentially expressed genes and proteins. Doxorubicin treatment induced dynamic remodeling of cardiac signaling, upregulating p53 signaling and apoptosis pathways, and significantly elevating plasma SERPINA3 in breast cancer patients.

synapsesocial.com/papers/6980fbbec1c9540dea80d779 https://doi.org/10.3390/ph19020234

Topics

Cardio-oncology

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Integrated Omics Approach to Delineate the Mechanisms of Doxorubicin-Induced Cardiotoxicity

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Integrated Omics Approach to Delineate the Mechanisms of Doxorubicin-Induced Cardiotoxicity

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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