Review article
Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies

https://doi.org/10.1016/j.yjmcc.2012.03.006Get rights and content
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Abstract

The utility of anthracycline antineoplastic agents in the clinic is compromised by the risk of cardiotoxicity. It has been calculated that approximately 10% of patients treated with doxorubicin or its derivatives will develop cardiac complications up to 10 years after the cessation of chemotherapy. Oxidative stress has been established as the primary cause of cardiotoxicity. However, interventions reducing oxidative stress have not been successful at reducing the incidence of cardiotoxicity in patients treated with doxorubicin. New insights into the cardiomyocyte response to oxidative stress demonstrate that underlying differences between in vitro and in vivo toxicities may modulate the response to superoxide radicals and related compounds. This has led to potentially new uses for pre-existing drugs and new avenues of exploration to find better pharmacotherapies and interventions for the prevention of cardiotoxicity. However, much work still must be done to validate the clinical utility of these new approaches and proposed mechanisms. In this review, the authors have reviewed the molecular mechanisms of the pathogenesis of acute and chronic doxorubicin-induced cardiotoxicity and propose potential pharmacological interventions and treatment options to prevent or reverse this specific type of heart failure.

Highlights

► The pathogenesis of doxorubicin-induced cardiotoxicity is complex and multifactorial. ► Oxidative stress is a major cause of doxorubicin-induced cardiotoxicity. ► Doxorubicin-induced heart failure can appear very late after the last administration. ► There is no specific curative or preventive treatment available.

Keywords

Doxorubicin
Anthracyclines
Cardiotoxicity
Heart failure
Oxidative stress
Cardioprotection

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