Current and proposed biomarkers of anthracycline cardiotoxicity in cancer: emerging opportunities in oxidative damage and autophagy

Abstract

A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or biological responses to a therapeutic intervention". Biomarkers can be utilized to detect disease, evaluate treatment risks, or determine treatment effectiveness. In the case of cancer, anthracyclines such as doxorubicin are front-line therapy to treat a number of different malignancies including breast cancer. However, a significant fraction of patients experience drug-induced cardiotoxicity. This toxicity is dose-limiting and can cause long-term morbidity or mortality. There is an unmet medical need to identify patients who are at risk for doxorubicin-induced cardiotoxicity, to detect cardiac damage early so that patient risk can be minimized, and to monitor the success of cardioprotective strategies. Therefore, doxorubicin treatment of cancer is an excellent example of the need for biomarkers to indicate drug safety in addition to drug efficacy. In this review we will discuss the mechanism of doxorubicinassociated cardiotoxicity, as well as other cancer therapies that induce cardiac toxicity by causing oxidative damage. We will also evaluate established and proposed biomarkers for cardiotoxicity based on our evolving knowledge of oxidative damage and subsequent autophagy. Finally, we will discuss advantages of combining oxidative damage- and autophagy-based protein biomarkers with current biomarkers such as troponins to facilitate early detection and mitigation of cardiotoxicity induced by cancer therapeutic agents.