A review of the relationship between Doxorubicin and Doxorubicinol, CBR1 polymorphism, and cardiotoxicity

Abstract

Background: Doxorubicin is a chemotherapy drug given to breast cancer patients. However, its administration is limited by its cardiotoxicity. The CBR1 enzyme in the liver catalyses doxorubicin to doxorubicinol, which also contributes to its cardiotoxicity. The polymorphism of the CBR1 enzyme affects doxorubicin and doxorubicinol levels in the body. Objective: To review the effect of CBR1 polymorphisms on the levels of doxorubicin and doxorubicinol after administration of doxorubicin. Methods: Relevant studies from selected databases were examined; Three main studies with 20 support studies were reviewed. Results: The recommended methods were the analysis of doxorubicin and doxorubicinol levels using the Dried Blood Spot biosampling technique, which uses the ultra-high-performance liquid chromatography-tandem mass spectrometry (LCMS/MS), and the evaluation of the genetic profile of CBR1 using Polymerase Chain Reaction. Conclusion: Four CBR1 genetic polymorphisms have been shown to reduce doxorubicinol levels in the body, which is associated with decreased CBR1 activity and expression. Thus, the conversion of doxorubicin to doxorubicinol is reduced. Therefore, individuals who experience CBR1 polymorphisms have a lower risk of cardiotoxicity after the administration of doxorubicin.