The Role of Biomarkers to Detect Cardiotoxicity with Cancer Therapy

Therapy with chemotherapeutics such as doxorubicin and targeted therapies such as trastuzumab and sunitinib are highly efficacious in the treatment of various malignancies.  However, in certain patients, these treatments can cause significant adverse effects on the cardiovascular system.  The potential impact on cardiovascular health is substantial, given the growing number of cancer patients of over 12.7 million individuals worldwide.  

Doxorubicin-induced cardiac damage occurs in 9% of treated patients at dosages of 250mg/m², and often carries a poor prognosis. The combination of doxorubicin and trastuzumab results in an increased incidence of cardiac injury, with 18-34% treated participants suffering from declines in cardiac function.  With sunitinib, the incidence of cardiac dysfunction ranges from 10 to 21% of treated individuals.

The current methods for the early identification and detection of patients who will suffer from cardiac dysfunction are limited, lacking sensitivity and specificity.  Work led by our research group has focused upon the discovery and application of novel and conventional cardiac biomarkers as diagnostic and prognostic tools in cancer therapy cardiotoxicity.  To accomplish these goals, we have built carefully phenotyped cohorts of patients receiving these therapies, and collected longitudinal blood samples, clinical data and cardiac testing at standard intervals.  We have quantified levels of circulating proteins in patients at multiple timepoints; defined the changes in these proteins over time; and determined the diagnostic and prognostic utility of single and multiple biomarkers as it relates to subsequent adverse cardiac events. Our ongoing work suggests that changes in biomarkers of oxidative stress (myeloperoxidase, growth differentiation factor-15), nitrosative stress (mono-methyl arginine), and vascular function (placental growth factor) with cancer therapy are associated with adverse cardiovascular outcomes in this population.  Our ultimate goals are to robustly identify cancer patients at high risk for adverse cardiovascular outcomes and improve our understanding of the underlying mechanisms of toxicity.  This work will improve the overall cardiovascular and oncologic health of a growing population.