Role of biomarkers in monitoring antiblastic cardiotoxicity

Abstract

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.

Drug Induced Cardiotoxicity: Mechanism, Prevention and Management

“…Understanding the mechanisms of anthracycline-induced cardiotoxicity is crucial for effective cardioprotection. Several complex mechanisms have been implicated including formation of iron complexes that can react with O 2 to form •O 2 −, which in turn dismutates to H 2 O 2 and/or enters the Haber-Weiss reaction, resulting in •OH, or can react with H 2 O 2 yielding directly •OH; increased production of reactive oxygen and reactive nitrogen species; lipid peroxidation; inflammation; induced cardiomyocyte apoptosis; interstitial fibrosis; abnormal signaling of epidermal growth factor as well as beta-arrestin; inhibition of nuclear topoisomerase II β; induced DNA damage; inhibition of vascular endothelial growth factor signaling; defective mitochondrial biogenesis; and calcium overloading [15,16,[19][20][21][22]. Mitochondria have an essential role in myocardial tissue homeostasis, and deterioration in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death and consequent cardiovascular dysfunction [4].…”

“…Anthracyclines are more likely to produce irreversible (type 1 drug-induced cardiotoxicity) microstructural lesions of cardiomyocytes leading to necrosis and apoptosis. Noteworthy, reversible (type 2) cardiotoxicity is associated with biological drugs targeting proteins regulating cancer cell proliferation which are also necessary for maintenance of cardiovascular homeostasis, and this toxicity can be resolved after completion of therapy or even during its continuation, and overlap as well as addition may occur between the types while using multiple potentially cardiotoxic drugs [16,22]. Noteworthy, some authors mention that reversible drug-induced cardiotoxic adverse effects are type 1 while irreversible ones are type 2 [2].…”

“…Left ventricular ejection fraction between 53 and 73% is considered normal [14]. Clinically manifested cardiotoxic effects may occur acutely at any time from the first dose of treatment till 2 weeks after it is terminated or chronically that may occur months after termination of treatment [15,16]. The frequency to recognize such complications with cancer patients has significantly increased during the past few decades due to increased survival of those patients which has accompanied the advances in drug treatment and health care, and early detection of drug-induced cardiotoxicity is of pivotal importance to avoid further deterioration of cardiac function [17].…”

Is it possible to cure childhood acute myeloid leukaemia without significant cardiotoxicity?

“…The major concern is to determine a cut-off point for positivity that maximizes the positive and negative predictive value Novo et al, 2016). Routine assessment of cardiac troponines or natriuretic peptides could provide additional information: however the benefits are as yet uncertain and the accuracy of biomarkers is an unresolved problem.…”

“…Routine assessment of cardiac troponines or natriuretic peptides could provide additional information: however the benefits are as yet uncertain and the accuracy of biomarkers is an unresolved problem. The major concern is to determine a cut-off point for positivity that maximizes the positive and negative predictive value Novo et al, 2016).…”