PT  - JOURNAL ARTICLE
AU  - Giorgio Minotti
TI  - Pharmacology at Work for Cardio-Oncology: Ranolazine to Treat Early Cardiotoxicity Induced by Antitumor Drugs
AID  - 10.1124/jpet.113.204057
DP  - 2013 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 343--349
VI  - 346
IP  - 3
4099  - http://jpet.aspetjournals.org/content/346/3/343.short
4100  - http://jpet.aspetjournals.org/content/346/3/343.full
SO  - J Pharmacol Exp Ther2013 Sep 01; 346
AB  - Antitumor drugs may cause asymptomatic diastolic dysfunction that introduces a lifetime risk of heart failure or myocardial infarction. Cardio-oncology is the discipline committed to the cardiac surveillance and management of cancer patients and survivors; however, cardio-oncology teams do not always attempt to treat early diastolic dysfunction. Common cardiovascular drugs, such as β blockers or angiotensin-converting enzyme inhibitors or others, would be of uncertain efficacy in diastolic dysfunction. This perspective describes the potential value of ranolazine, an antianginal drug that improves myocardial perfusion by relieving diastolic wall tension and dysfunction. Ranolazine acts by inhibiting the late inward sodium current, and pharmacological reasonings anticipate that antitumor anthracyclines and nonanthracycline chemotherapeutics might well induce anomalous activation of this current. These notions formed the rationale for a clinical study of the efficacy and safety of ranolazine in cancer patients. This study was not designed to demonstrate that ranolazine reduced the lifetime risk of cardiac events; it was designed as a short term proof-of-concept study that probed the following hypotheses: 1) asymptomatic diastolic dysfunction could be detected a few days after patients completed antitumor therapy, and 2) ranolazine was active and safe in relieving echocardiographic and/or biohumoral indices of diastolic dysfunction, measured at 5 weeks or 6 months of ranolazine administration. These facts illustrate the translational value of pharmacology, which goes from identifying therapeutic opportunities to validating hypotheses in clinical settings. Pharmacology is a key to the success of cardio-oncology.