MicroRNAs in Cancer Treatment-Induced Cardiotoxicity

Abstract

Cancer treatment has made significant progress in the cure of different types of tumors. Nevertheless, its clinical use is limited by unwanted cardiotoxicity. Aside from the conventional chemotherapy approaches, even the most newly developed, i.e., molecularly targeted therapy and immunotherapy, exhibit a similar frequency and severity of toxicities that range from subclinical ventricular dysfunction to severe cardiomyopathy and, ultimately, congestive heart failure. Specific mechanisms leading to cardiotoxicity still remain to be elucidated. For instance, oxidative stress and DNA damage are considered key players in mediating cardiotoxicity in different treatments. microRNAs (miRNAs) act as key regulators in cell proliferation, cell death, apoptosis, and cell differentiation. Their dysregulation has been associated with adverse cardiac remodeling and toxicity. This review provides an overview of the cardiotoxicity induced by different oncologic treatments and potential miRNAs involved in this effect that could be used as possible therapeutic targets.

Keywords: cancer therapy; cardiotoxicity; cardiovascular diseases; microRNAs.

Figure 1

Mechanisms of cardiotoxicity induced by different classes of anticancer therapies. Treatment for cancer diseases can adversely affect both the heart and the vasculature, leading to death of cardiomyocytes, endothelial dysfunction, and, consequently, different cardiovascular complications. Common cellular targets and pathways involved in cardiotoxicity linked to anthracyclines (A), ErbB2 inhibitors (B), VEGF inhibitors (C), anti-BCR-Abl agents (D), radiation therapy and immunotherapy (in particular checkpoint inhibitors) (E), and other commonly used, less specific antineoplastic drugs (antimetabolites, proteasome inhibitors, and taxanes) (F) are schematically illustrated. Abbreviations: ANTs, anthracyclines; TopIIβ, topoisomerase IIβ; ROS, reactive oxygen species; RNS, reactive nitrogen species; LV, left ventricular; RV, right ventricular; HF, heart failure; ErbB2/ErbB4, human epidermal growth factor receptor 2/4; VEGF, vascular endothelial growth factor; R, receptor; TKs, tyrosine kinases; TKIs, tyrosine kinase inhibitors; ER, endoplasmic reticulum; PAD, peripheral artery disease; PD-1, programmed cell death protein 1; PD-L1, programmed cell death protein ligand 1.