Cardiotoxicity of doxorubicin – causes, prevention, prospects
DOI:
https://doi.org/10.12775/JEHS.2022.12.11.035Keywords
Doxorubicin, Anthracyclines, cardiotoxicity, cardiomyopathy, chemotherapyAbstract
Introduction: Doxorubicin is one of the most reliable anthracycline chemotherapeutics. Its high efficacy in treating a large range of cancers, however, comes hand in hand with complications. A hallmark of anthracycline drugs, and also their most common side effect, is heart failure caused by the development of dilated cardiomyopathy.
Purpose of the study: The purpose of our work is to present the current state of knowledge about the causes of doxorubicin cardiotoxicity and to present known ways to minimize the negative impact on the patient's health.
Materials and Methods: We performed a non-systematic review of the Polish and English-language literature available in the database, using the keywords: ,,doxorubicin"; ,,anthracyclines"; ,,cardiotoxicity"; ,,cardiomyopathy"; ,,chemotherapy".
Results: Doxorubicin is counted among the first-generation anthracycline cytostatics widely used in cancer chemotherapy. The enormous potential of anthracyclines is a motivator for further attempts to improve these molecules and eliminate side effects. The methods developed so far have led to a reduction in the frequency of cardiovascular incidents, but the risks associated with the use of these drugs are still relatively high and the cost of liposomal forms is high.
Summary: The current state of knowledge identifies promising options for improving the well-being of patients undergoing treatment with chemotherapeutic agents. Hopes for effective analogs free of cardiotoxic effects are reasonable, and the use of companion substances is an additional possibility.
References
Arcamone F, Cassinelli G, Fantini G, et al. Adriamycin, 14‐hydroxydaunomycin, a new antitumor antibiotic from S. Peucetius var. caesius. Biotechnol Bioeng. 1969;11(6):1101-1110. doi:10.1002/bit.260110607
Minotti G. Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity. Pharmacol Rev. 2004;56(2):185-229. doi:10.1124/pr.56.2.6
Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther. 2014;10(4):853- 858. doi:10.4103/0973-1482.139267
Gewirtz D. A critical evaluation of the mechanisms of action proposed for the antitumour effects of the anthracycline antibiotics adriamycin and daunomycin. Biochem Pharmacol. 1999;57(98):727-741.
Pang B, Qiao X, Janssen L, et al. Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nat Commun. 2013;4:1908. doi:10.1038/ncomms2921
Long BH, Willis CE, Prestayko AW, Crooke ST. Effect of anthracycline analogues on the appearance of newly synthesized total RNA and messenger RNA in the cytoplasm of erythroleukemia cells. Mol Pharmacol. 1982;22(1).
McGowan J V., Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline Chemotherapy and Cardiotoxicity. Cardiovasc Drugs Ther. 2017;31(1):63-75. doi:10.1007/s10557-016-6711-0
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869-2879. doi:10.1002/CNCR.11407
Mollova M, Bersell K, Walsh S, et al. Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci USA. 2013;110(4):1446-1451. doi:10.1073/PNAS.1214608110/SUPPL_FILE/SM06.MOV
Cervantes A, Pinedo HM, Lankelma J, Schuurhuis GJ. The role of oxygen-derived free radicals in the cytotoxicity of doxorubicin in multidrug resistant and sensitive human ovarian cancer cells. Cancer Lett. 1988;41(2):169-177. doi:10.1016/0304-3835(88)90113-9
Keizer HG, Pinedo HM, Schuurhuis GJ, Joenje H. Doxorubicin (adriamycin): A critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacol Ther. 1990;47(2):219-231. doi:10.1016/0163- 7258(90)90088-J
Turley H, Comley M, Houlbrook S, et al. The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. Br J Cancer. 1997;75(9):1340. doi:10.1038/BJC.1997.227
Henriksen PA. Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention. Heart. 2018;104(12):971-977. doi:10.1136/heartjnl-2017-312103
Vejpongsa P, Yeh ETH. Topoisomerase 2β: a promising molecular target for primary prevention of anthracycline-induced cardiotoxicity. Clin Pharmacol Ther. 2014;95(1):45-52. doi:10.1038/CLPT.2013.201
Pang B, Qiao X, Janssen L, et al. Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nat Commun. 2013;4(May):1908-1913. doi:10.1038/ncomms2921
Qiao X, Van Der Zanden SY, Wander DPA, et al. Uncoupling DNA damage from chromatin damage to detoxify doxorubicin. Proc Natl Acad Sci USA. 2020;117(26):15182-15192. doi:10.1073/pnas.1922072117
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