Thinking Outside the Therapeutic Box: The Potential of Polyphenols in Preventing Chemotherapy-Induced Endothelial Dysfunction

The numerous side effects and adverse health implications associated with chemotherapies have long plagued the field of cancer care. Whilst in some cases a curative measure, this highly toxic intervention consistently scores poorly on quantitative measures of tolerability and safety. Of these side effects, cardiac and microvascular defects pose the greatest health risk and are the leading cause of death amongst cancer survivors who do not succumb to relapse. In fact, in many low-grade cancers, the risk of recurrence is far outweighed by the cardiovascular risk of morbidity. As such, there is a pressing need to improve outcomes within these populations. Polyphenols are a group of naturally occurring metabolites that have shown potential vasoprotective effects. Studies suggest they possess antioxidant and anti-inflammatory activities, in addition to directly modulating vascular signalling pathways and gene expression. Leveraging these properties may help counteract the vascular toxicity induced by chemotherapy. In this review, we outline the main mechanisms by which the endothelium is damaged by chemotherapeutic agents and discuss the ability of polyphenols to counteract such side effects. We suggest future considerations that may help overcome some of the published limitations of these compounds that have stalled their clinical success. Finally, we briefly explore their pharmacological properties and how novel approaches could enhance their efficacy while minimising treatment-related side effects.