NOS3 and endothelial dysfunction: Kanduri et al. proposed multiple mechanisms for CTX associated with fluoropyrimidines like 5-Fluorouracil (-FU) or its prodrug, capecitabine, including myocardial ischaemia mediated by endothelial dysfunction, causing decreased NO release, platelet aggregation, fibrin formation, followed by coronary vasospasm induced by vasoconstriction; as well as direct cardiomyocyte injury caused by fluorocitrate, a cardiotoxic metabolite of 5-FU, which increases ROS production and inhibits antioxidant protective functions (82), potentially leading to further dysfunction in eNOS activity and NO production.