Translational aspects of doxorubicin-induced cardiotoxicity: What we have omitted for the past decades?

Area of Science:

• Cardio-oncology
• Translational Medicine
• Pharmacology

Background:

• Anthracyclines are vital cancer treatments but cause dose-dependent cardiotoxicity.
• Doxorubicin (DOX)-induced cardiovascular toxicity mechanisms include oxidative stress, mitochondrial dysfunction, DNA damage, and ferroptosis.
• Existing animal models for DOX cardiotoxicity have limitations in replicating chronic human conditions and specific patient factors.

Purpose of the Study:

• To review the translational challenges in studying doxorubicin-induced cardiotoxicity.
• To elucidate factors hindering the translation of experimental findings into clinical applications for cardioprotective strategies.

Main Methods:

• Review of existing literature on animal models of doxorubicin cardiotoxicity.
• Analysis of species-specific variations, model limitations (acute vs. chronic), and underrepresentation of patient-specific factors.
• Exploration of challenges in developing cardioprotective strategies in cardio-oncology.

Main Results:

• Acute animal models for DOX cardiotoxicity are limited in replicating chronic human cardiomyopathy.
• Chronic models offer better clinical relevance but present logistical difficulties.
• Species-specific differences, lack of comorbid conditions, combination chemotherapy, and underrepresentation of sex/age responses complicate extrapolation.

Conclusions:

• Translating findings from animal models of DOX cardiotoxicity to human clinical applications remains a significant hurdle.
• Addressing limitations in current models is critical for developing effective, personalized cardioprotective strategies.
• Improved models are essential for advancing cardio-oncology and mitigating anthracycline-induced heart damage.