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Review
. 2017 Feb;31(1):63-75.
doi: 10.1007/s10557-016-6711-0.

Anthracycline Chemotherapy and Cardiotoxicity

Affiliations
Review

Anthracycline Chemotherapy and Cardiotoxicity

John V McGowan et al. Cardiovasc Drugs Ther. 2017 Feb.

Abstract

Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today's anthracycline-treated cancer patients may become tomorrow's cardiac patient.

Keywords: Cancer anthracycline doxorubicin chemotherapy cardiotoxicity cardioprotection.

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Conflict of interest statement

Conflict of Interest

All authors (JVM, RC, AM, IP, JMW, DMY) declare that they have no conflicts of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Funding

This article does not contain any studies conducted by the authors and thus there are no direct funding disclosures. Two authors (RC, IP) were supported by funding from the Biomedical Research Centre (grant number BRC233/CM/SD/101320). This manuscript was undertaken at University College London Hospitals / University College London (UCLH/UCL) who received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme.

Informed Consent

Not applicable to this article-- as this article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
The four anthracycline derivatives Doxorubicn (DOX), Daunarubicin (DNR), Epirubicin (EPI) and Idarubicin (IDA). The anthracyclines share a tetracyclic aglycone structure of four cyclohexane chains with a daunosamine sugar moiety at carbon C7 of ring a; adjacent quinone-hydroquinone groups in rings b and c; a methoxy substituent carbon C4 in ring D; a carbonyl group at C13; and a short side chain in C9. Doxorubicin and daunorubicin differ in their short chains. Doxorubicin has a primary alcohol, whereas daunorubicin has a methyl group. Epirubicin is derived from doxorubicin by axial-to-equitorial epimerisation of the hydroxyl group in the daunosamine moiety. Idarubicin is identical to daunorubicin except the 4-methoxy group in ring D is removed
Fig. 2
Fig. 2
Doxorubicin staining shows sequestration in (L) cardiomyocytes and (R) malignant cervical cancer cells (courtesy Dr. I Piotrowska)

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