Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance

J Oncol Pharm Pract. 2020 Mar;26(2):434-444. doi: 10.1177/1078155219877931. Epub 2019 Oct 9.

Abstract

Background: Doxorubicin is one of the most commonly prescribed and time-tested anticancer drugs. Although being considered as a first line drug in different types of cancers, the two main obstacles to doxorubicin therapy are drug-induced cardiotoxicity and drug resistance.

Method: The study utilizes systemic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar, and Cochrane. The study utilizes secondary information obtained from health organizations using filters and keywords to sustain information relevancy. The study utilizes information retrieved from studies captured in the peer-reviewed journals on "doxorubicin-induced cardiotoxicity" and "doxorubicin resistance."

Discussion and results: The exact mechanisms of cardiotoxicity are not known; various hypotheses are studied. Doxorubicin can lead to free radical generation in various ways. The commonly proposed underlying mechanisms promoting doxorubicin resistance are the expression of multidrug resistance proteins as well as other causes.

Conclusion: In this review, we have described the major obstacles to doxorubicin therapy, doxorubicin-induced cardiotoxicity as well as the mechanisms of cancer drug resistance and in following the treatment failures.

Keywords: Doxorubicin; cancer; cardiotoxicity; multidrug resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / therapeutic use
  • Cardiotoxicity
  • Cardiotoxins / adverse effects*
  • Cardiotoxins / therapeutic use
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / diagnosis
  • Doxorubicin / adverse effects*
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / physiology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Humans
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*

Substances

  • Antibiotics, Antineoplastic
  • Cardiotoxins
  • Doxorubicin