Pharmacological foundations of cardio-oncology

Anthracyclines and many other antitumor drugs induce cardiotoxicity that occurs "on treatment" or long after completing chemotherapy. Dose reductions limit the incidence of early cardiac events but not that of delayed sequelae, possibly indicating that any dose level of antitumor drugs would prime the heart to damage from sequential stressors. Drugs targeted at tumor-specific moieties raised hope for improving the cardiovascular safety of antitumor therapies; unfortunately, however, many such drugs proved unable to spare the heart, aggravated cardiotoxicity induced by anthracyclines, or were safe in selected patients of clinical trials but not in the general population. Cardio-oncology is the discipline aimed at monitoring the cardiovascular safety of antitumor therapies. Although popularly perceived as a clinical discipline that brings oncologists and cardiologists working together, cardio-oncology is in fact a pharmacology-oriented translational discipline. The cardiovascular performance of survivors of cancer will only improve if clinicians joined pharmacologists in the search for new predictive models of cardiotoxicity or mechanistic approaches to explain how a given drug might switch from causing systolic failure to inducing ischemia. The lifetime risk of cardiotoxicity from antitumor drugs needs to be reconciled with the identification of long-lasting pharmacological signatures that overlap with comorbidities. Research on targeted drugs should be reshaped to appreciate that the terminal ballistics of new "magic bullets" might involve cardiomyocytes as innocent bystanders. Finally, the concepts of prevention and treatment need to be tailored to the notion that late-onset cardiotoxicity builds on early asymptomatic cardiotoxicity. The heart of cardio-oncology rests with such pharmacological foundations.