Soluble neprilysin and the translational continuum in cardio-oncology

In cardio-oncology, the gap between mechanistic studies and pharmacological trials impedes the delineation of effective cardioprotective strategies. The angiotensin-receptor/neprilysin inhibitor (ARNI) have shown beneficial effects in patients with heart failure with reduced ejection fraction, but failed to show significant benefit in cardio-oncology. In a preclinical model, soluble neprilysin levels (sNEP) tracked anthracycline-induced myocardial damage and systolic dysfunction and sNEP levels may predict benefits of ARNI. The neutral results of clinical trials testing sacubitril/valsartan in this setting underscore the challenge of bridging pre-clinical knowledge to patients' management and call for clinical trials in precision medicine approaches in which biomarkers (i.e. sNEP) may guide treatment (i.e. ARNI).