The Role of Biomarkers in Cardio-Oncology

Abstract

In the field of cardio-oncology, it is well recognised that despite the benefits of chemotherapy in treating and possibly curing cancer, it can cause catastrophic damage to bystander tissues resulting in a range of potentially of life-threatening cardiovascular toxicities, and leading to a number of damaging side effects including heart failure and myocardial infarction. Cardiotoxicity is responsible for significant morbidity and mortality in the long-term in oncology patients, specifically due to left ventricular dysfunction. There is increasing emphasis on the early use of biomarkers in order to detect the cardiotoxicity at a stage before it becomes irreversible. The most important markers of cardiac injury are cardiac troponin and natriuretic peptides, whilst markers of inflammation such as interleukin-6, C-reactive protein, myeloperoxidase, Galectin-3, growth differentiation factor-15 are under investigation for their use in detecting cardiotoxicity early. In addition, microRNAs, genome-wide association studies and proteomics are being studied as novel markers of cardiovascular injury or inflammation. The aim of this literature review is to discuss the evidence base behind the use of these biomarkers for the detection of cardiotoxicity.

Keywords: BNP; Biomarker; Brain natriuretic peptide; Cardio-Oncology; Cardiotoxicity; Heart failure; Troponin.

Fig. 1

Demonstrates the main mechanism of cardiotoxicity for most cytotoxic chemotherapy. Firstly, anthracycylines have direct mechanisms of damaging DNA resulting in cell cycle arrest leading to either: apopotosis, cell necrosis or cell autophagy. They also generate toxic reactive oxygen species (ROS). ROS trigger off a cascade of events which alters mitochondrial permeability and hence function which moderates calcium signalling and hence myocyte contraction. The mechansim of this invovles the SERCA2a protein which is at the centre of calcium homeostasis. Secondly the receptor tyrosine kinase inhibitors, namely bevacluzumab, trastuzumab, etc. function by inhibiting the activity of their receptor proteins: Vascular Endothelial Growth Factor Receptor (VEGFR), ErBb4/ErBb2 and Her2/Neu receptor resulting in cell cycle arrest in the Growth 1 (G1) phase of the cycle leading eventually to apoptosis, necrosis or cell autophagy. This transition is mediated by p53 (a nuclear DNA-binding phosphoprotein). [22, 155, 156]