Neprilysin Inhibition in the Prevention of Anthracycline-Induced Cardiotoxicity

Area of Science:

• Cardiology
• Oncology
• Pharmacology

Background:

• Anthracycline-induced cardiotoxicity (AIC) is a significant clinical challenge in cancer patients, leading to myocardial dysfunction.
• AIC mechanisms include cardiomyocyte DNA damage, oxidative stress, mitochondrial dysfunction, and renin-angiotensin-aldosterone system (RAAS) dysregulation.
• Angiotensin receptor/neprilysin inhibitors (ARNi) are established treatments for heart failure with reduced ejection fraction.

Purpose of the Study:

• To review the potential of ARNi in preventing anthracycline-induced cardiotoxicity (AIC).
• To summarize preclinical findings on ARNi's cardioprotective effects relevant to AIC.
• To highlight ongoing clinical trials investigating ARNi for AIC prevention.

Main Methods:

• Review of preclinical studies and clinical trial data concerning ARNi and AIC.
• Analysis of ARNi's proposed mechanisms of action in preventing cardiotoxicity.
• Inclusion of data from the ongoing PRADAII trial.

Main Results:

• Preclinical studies indicate ARNi administration prevents ventricular systolic dysfunction and electrocardiographic changes in animal models of AIC.
• ARNi ameliorates oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and inflammation associated with anthracyclines.
• The PRADAII trial is actively assessing ARNi efficacy in breast cancer patients undergoing treatment.

Conclusions:

• ARNi demonstrate significant potential for preventing anthracycline-induced cardiotoxicity based on preclinical evidence.
• Further clinical investigation, such as the PRADAII trial, is crucial to confirm ARNi's efficacy in cancer patients.
• ARNi may offer a novel therapeutic strategy to mitigate AIC and improve outcomes for cancer survivors.