Abstract

Anthracycline-induced cardiotoxicity (AIC) persists as a significant cause of morbidity and mortality in cancer survivors. Although many protective strategies have been evaluated, cardiotoxicity remains an ongoing threat. The mechanisms of AIC remain unclear; however, several pathways have been proposed, suggesting a multifactorial origin. When the central role of topoisomerase 2β in the pathophysiology of AIC was described some years ago, the classical reactive oxygen species (ROS) hypothesis shifted to a secondary position. However, new insights have reemphasized the importance of the role of oxidative stress-mediated signaling as a common pathway and a critical modulator of the different mechanisms involved in AIC. A better understanding of the mechanisms of cardiotoxicity is crucial for the development of treatment strategies. It has been suggested that the available therapeutic interventions for AIC could act on the modulation of oxidative balance, leading to a reduction in oxidative stress injury. These indirect antioxidant effects make them an option for the primary prevention of AIC. In this review, our objective is to provide an update of the accumulated knowledge on the role of oxidative stress in AIC and the modulation of the redox balance by potential preventive strategies.

Highlights

  • Over the past two decades, there have been significant improvements in the early detection and pharmacological treatment of cancer, leading to a dramatic increase in survivorship [1] [2]

  • This analysis revealed that polymorphisms in three genes were significantly associated with an increased odds of cardiotoxicity in individuals treated with anthracyclines, and two of them were associated with oxidative stress: CYBA and RAC2 genes [53]

  • According to basic and preclinical studies, the spironolactone antioxidant effects have been associated with nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition [101, 102], and enalapril oxidative stress abrogation has been associated with an enhancement of intracellular antioxidant defences [99, 100]

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Summary

Introduction

Over the past two decades, there have been significant improvements in the early detection and pharmacological treatment of cancer, leading to a dramatic increase in survivorship [1] [2]. This improvement in the life expectancy of cancer patients has led to an increase in the pool of patients at risk of experiencing long-term chemotherapyrelated side effects. Been limited by the development of cardiotoxicity in a cumulative dosedependent manner [4] This side effect impacts the longterm prognosis of patients treated successfully from an oncological point of view [5]. The objective of this review is to provide an update on the accumulated knowledge regarding the early and critical role of oxidative stress in the damage mechanisms of AIC and discuss the potential benefits of preventive strategies that reduce oxidative stress damage through lifestyle changes, physical exercise, and pharmacological therapies to reduce risk factors and environmental stressors

Mechanisms of AnthracyclineInduced Cardiotoxicity
Convergence of “Redox Cycling” and “Topoisomerase 2β” Hypotheses
Beta-Blockers with Antioxidant Properties
Dexrazoxane
New Potential Interventions
Combined Strategies
Findings
Conclusions
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