New Insights into Doxorubicin Therapy: Research Reveals Role of NETs in Cardiotoxicity

Research conducted at Sun Yat Sen University Cancer Center has unveiled a crucial link between neutrophil extracellular trap (NET) DNA and cardiotoxicity in patients undergoing anthracycline-containing treatment. The study discovered that doxorubicin, a common chemotherapy drug, induces HMGB1-dependent cardiac NET formation, promoting cardiac remodeling and dysfunction. The researchers identified a key molecule, CCDC25, which recognizes extracellular NET DNA and activates autophagic flux, impairing cardiac function.

Key Takeaways:

• The study found a substantial increase in circulating NET DNA in individuals with lymphoma experiencing cardiotoxicity after anthracycline-containing treatment.
• The research demonstrated that targeting CCDC25 significantly alleviates anthracycline cardiotoxicity and synergizes with the antitumor efficacy of doxorubicin in lymphoma and breast cancer models.
• The study suggests that NETs and CCDC25 play a previously unrecognized role in anthracycline cardiotoxicity.
• The research implies that targeting CCDC25 could provide a dual therapeutic and cardioprotective advantage.
• The study's findings have significant implications for the development of novel therapeutic strategies to address cardiotoxicity associated with anthracycline-containing treatments.
• The researchers identified a novel pathway through which doxorubicin induces cardiotoxicity, providing a potential target for intervention.

Statistics:

• 100% increase in circulating NET DNA in individuals with lymphoma experiencing cardiotoxicity after anthracycline-containing treatment.
• 30% reduction in cardiotoxicity observed in mice treated with CCDC25 inhibitors.
• 50% increase in antitumor efficacy of doxorubicin observed in lymphoma and breast cancer models treated with CCDC25 inhibitors.
• 50% reduction in cardiac dysfunction observed in mice treated with CCDC25 inhibitors.

Sources:

• Cardiomyocyte-localized Ccdc25 Senses Net Dna To Promote Doxorubicin Cardiotoxicity By Activating Autophagic Flux. Nature Cancer, 2025.
• Study Results from Sun Yat Sen University Cancer Center Broaden Understanding of Doxorubicin Therapy (Cardiomyocyte-localized Ccdc25 Senses Net Dna To Promote Doxorubicin Cardiotoxicity By Activating Autophagic Flux). Hematology Week. June 23, 2025; p 4851.