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Doxorubicin-induced cardiotoxicity: causative factors and possible interventions

Jones, Isobel C, Dass, Crispin R·2022·Journal of Pharmacy and Pharmacology
DOI 10.1093/jpp/rgac063
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Abstract

Objectives: Doxorubicin (Dox) belongs to the anthracycline drug classification and is a widely administered chemotherapeutic. However, Dox use in therapy is limited by its cardiotoxicity, representing a significant drawback of Dox treatment applicability. A large amount of current research is on reducing Dox-induced cardiotoxicity by developing targeted delivery systems and investigating cardiotoxicity mechanisms. Recently, discrepancies have challenged the traditional understanding of Dox metabolism, mechanisms of action and cardiotoxicity drivers. This review summarises the current knowledge around Dox’s metabolism, mechanisms of anticancer activity, and delivery systems and offers a unique perspective on the relationships between several proposed mechanisms of Dox-induced cardiotoxicity. Key findings: While there is a strong understanding of Dox’s pharmacokinetic properties, it is unclear which enzymes contribute to Dox metabolism and how Dox induces its cytotoxic effect in neoplastic and non-neoplastic cells. Evidence suggests that there are several potentially synergistic mechanisms involved in Dox-induced cardiotoxicity. Summary: It has become clear that Dox operates in a multifactorial fashion dependent on cellular context. Accumulation of oxidative stress appears to be a common factor in cardiotoxicity mechanisms, highlighting the importance of novel delivery systems and antioxidant therapies.

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Metadata

Authors
Jones, I. C., & Dass, C. R.
Venue
Journal of Pharmacy and Pharmacology
Publisher
Oxford University Press (OUP)
Published
2022-08-22
Volume
74
Issue
12
Pages
1677-1688
ISSN
  • 0022-3573
  • 2042-7158
DOI
10.1093/jpp/rgac063
Cited by
91
References
2
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)

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