Prevention of Anthracycline-Induced Cardiotoxicity

Abstract

Anthracycline compounds are major culprits in chemotherapy-induced cardiotoxicity, which is the chief limiting factor in delivering optimal chemotherapy to cancer patients. Although extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity, there is little consensus regarding the best approach. Recent advances in basic mechanisms of anthracycline-induced cardiotoxicity provided a unified theory to explain the old reactive-oxygen species hypothesis and identified topoisomerase 2β as the primary molecular target for cardioprotection. This review outlines current strategies for primary and secondary prevention of anthracycline-induced cardiotoxicity resulting from newly recognized molecular mechanisms and identifies knowledge gaps requiring further investigation.

Integrating cardiomyocytes from human pluripotent stem cells in safety pharmacology: has the time come?

“…The resulting contractile and electrical dysfunction often leads to abnormal heartbeat and life‐threatening arrhythmias (Ewer and Ewer, 2015; Gintant et al , 2016). Arrhythmia is currently an immense burden on public health, with millions of people at risk of heart malfunction because of the cardiotoxic effects of drugs (Rubinstein and Camm, 2002; Vejpongsa and Yeh, 2014; Viskin et al , 2015). Individuals with an underlying but undiagnosed genetic risk may be especially vulnerable because their need for safer alternatives already on the market may be unrecognized (Svanström et al , 2014; Schwartz and Woosley, 2016).…”

Modern View on Cardiotoxicity of Chemotherapeutics in Oncology Including Anthracyclines

“…При этом, удаление из сердца мышей Top2b защищает их от развития АКМП. Гемохроматоз, напротив, усиливает действие Top2b, способствуя увеличению продукции ROS [11]. Следует также сказать, что антрациклиновые антибиотики используются преимущественно в составе различных схем химиотерапии, а не как монотерапия.…”

“…Использовании кардиопротективных агентов: дексразоксана, бета-блокаторов, ингибиторов АПФ, блокаторов рецепторов ангиотензина II на фоне полихимиотерапии [11].…”

Anthracycline Cardiotoxicity: Strategies for Prevention and Intervention

“…1,2 However, despite efforts towards cardioprotective strategies and early detection of anthracycline cardiotoxicity, defined as decline in Left Ventricular Ejection Fraction (LVEF) of ≥10% from baseline or to <50%, 3,4 there is currently no consensus on the optimal approach. Current clinical practice guidelines recommend serial LVEF monitoring to identify cardiotoxicity in high-risk patients receiving anthracyclines; 3,4 however, it has come to light that LVEF reduction may be a late manifestation of cardiotoxicity, 5,6 with potentially limited prospects for reversibility.…”

“…19,[21][22][23][24] Strategies to mitigate anthracycline cardiotoxicity may be classified as pre-emptive (primary prevention) versus reactive (secondary prevention). 2 For primary prevention, conventional treatments for heart failure, including beta-blockers and angiotensin antagonists, have been evaluated, with promising results in recent meta-analyses. 25,26 In the recently completed PRADA study, a randomized controlled trial comparing primary prevention of cardiotoxicity with metoprolol, candesartan, versus matched placebos in 120 patients treated with anthracyclines with or without trastuzumab for early breast cancer, 27,28 pre-emptive candesartan was shown to result in a statistically significantly attenuation in LVEF decline.…”