Title:Current and Proposed Biomarkers of Anthracycline Cardiotoxicity in Cancer: Emerging Opportunities in Oxidative Damage and Autophagy
Volume: 12
Issue: 6
Author(s): J. S. Dickey and V. A. Rao
Affiliation:
Keywords:
Autophagy, doxorubicin, oxidative stress, protein oxidation, reactive oxygen species, troponin, biomarker, malignancy, pharmaceuticals, therapeutics, indenoisoquinoline activity, chemotherapy, drug efficacy, chemotherapeutic agents, cardiotoxicity
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.
