Role of biomarkers in monitoring antiblastic cardiotoxicity Giuseppina Novo a , Christian Cadeddu b , Vincenzo Sucato a , Pasquale Pagliaro c , Silvio Romano d , Carlo G. Tocchetti e , Concetta Zito f , Luca Longobardo f , Savina Nodari g and Maria Penco d Early detection of anticancer drug-induced cardiotoxicity (CTX) has been evaluated by most international scientific cardiology and oncology societies. High expectations have been placed on the use of specific biomarkers. In recent years, conventional biomarkers and molecules of more recent interest have been tested and compared in the context of anticancer drug-related CTX. Encouraging results were obtained from studies on molecules of myocardial damage, such as troponin and markers of myocardial wall stress, including circulating natriuretic peptides, as well as from the assessment of the products of inflammation or circulating levels of free radicals. However, clear guidelines on their sensitivity, specificity, and accuracy are not yet available, and many challenges, such as the optimal time of assessing, optimal schedule for evaluation, optimal cut-off point for positivity with the highest level of specificity, and optimal comparability of different assays for the measurements, remain unresolved. Given the importance of having a reliable and accurate tool for monitoring anticancer drug-induced CTX, this review will focus on the available data on the most effective and widely used biomarkers and the studies that are currently underway that aim to identify the effectiveness of new approaches in this therapeutic setting. J Cardiovasc Med 2016, 17 (suppl 1):e27–e34 Keywords: antineoplastic, antiblastic, anticancer drugs, biomarkers, brain natriuretic peptide, cardiac toxicity, troponin a Department of Internal Medicine and Specialties (DIBIMIS), Chair of Cardiology, University of Palermo, Palermo Italy, b Department of Medical Sciences ‘Mario Aresu’, University of Cagliari, Cagliari Italy, c Department of Clinical and Biological Sciences, University of Turin, Orbassano Italy, d Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy, e Department of Translational Medical Sciences, University of Napoli Federico II, Naples Italy, f Department of Clinical and Experimental Medicine. Section of Cardiology, University of Messina, Messina Italy and g Department of Clinical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, Brescia, Italy Correspondence to Prof. Giuseppina Novo, Department of Internal Medicine and Specialities (DIBIMIS), Chair of Cardiology, University of Palermo, Palermo Italy, Tel: +0039 0916554303; e-mail: giuseppina.novo@unipa.it Received 27 January 2016 Introduction Anticancer drug-induced cardiotoxicity (CTX) is a major health problem that is growing because of the wider use of antineoplastic therapies within the last few decades. CTX includes a broad spectrum of cardiac effects, such as arrhythmias, thromboembolism, and cardiomyopathy. Its true incidence is unclear; however, some researchers have reported it to be as high as 50–65% of survivors. 1,2 Many drugs may cause an impairment of heart function; in particular, anthracyclines are potent antitumour agents that are used in a large spectrum of malignancies. Other cytotoxic drugs that determine CTX include 5-fluorour- acil, capecitabine, mitoxantrone, cisplatin, taxoids paclitaxel, and docetaxel. Newer biological drugs that can induce CTX are the monoclonal anti-ErbB2 antibody trastuzumab and tyrosine-kinase inhibitors (TKI). 3–7 Anticancer drug-induced CTX are traditionally distin- guished as ‘acute CTX’, in which damage can develop at any time from the initiation of antineoplastic treatments up to 2 weeks after termination of treatment, and ‘chronic CTX’, which can be categorized into two types based on the timing of the onset of clinical symptoms: early chronic, within 1 year from the termination of chemother- apy, and late chronic CTX, after 1 year. The most common form of antineoplastic drug-induced CTX is left ventricular (LV) dysfunction, which may be subclinical (or asymptomatic), but can also lead to severe heart failure. 8–14 Based on its severity and reversibility, two classes of anticancer drug-induced CTX have been proposed: type 1 CTX, consisting of a microstructural lesion of cardiomyocytes, can result in cell death by necrosis or apoptosis and is mostly considered irreversible and classically attributed to anthracyclines 15 ; type 2 CTX relates to cardiac dys- function without significant microstructural lesions 16–19 and can be resolved after completion of therapy or sometimes during its continuation, and it is attributed to biological drugs that are designed to target-specific proteins that regulate cancer cell proliferation. This CTX occurs because the same target proteins are expressed in the cardiovascular system and are necess- ary for the maintenance of cardiovascular homeostasis. Nevertheless, these two forms of toxicity may overlap; for example, trastuzumab, an anti-ErbB2 antibody, can result Supplement Submission 1558-2027 ß 2016 Italian Federation of Cardiology. All rights reserved. DOI:10.2459/JCM.0000000000000379 © 2016 Italian Federation of Cardiology. All rights reserved.