Key result
CBR1 polymorphisms are linked to decreased doxorubicin cardiotoxicity risk by reducing conversion to doxorubicinol.
Why the study?
Doxorubicin use in breast cancer is limited by cardiotoxicity, and CBR1 converts doxorubicin to cardiotoxic doxorubicinol, with CBR1 polymorphisms potentially affecting these drug levels.
Do CBR1 polymorphisms reduce the risk of cardiotoxicity in breast cancer patients receiving doxorubicin?
Do CBR1 polymorphisms reduce the risk of cardiotoxicity in breast cancer patients receiving doxorubicin?
CBR1 genetic polymorphisms reduce the conversion of doxorubicin to its more cardiotoxic metabolite doxorubicinol, thereby lowering the risk of doxorubicin-induced cardiotoxicity in breast cancer patients.
Answers are grounded in this paper and cite their sources.
May inform CBR1-guided risk stratification for doxorubicin cardiotoxicity; leaves open prospective validation before clinical use.
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.
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Rahmani et al. (2024) conducted a review in Breast cancer and doxorubicin-induced cardiotoxicity. CBR1 polymorphism vs. Wild-type CBR1 was evaluated on Doxorubicinol levels and cardiotoxicity risk. CBR1 genetic polymorphisms reduce the conversion of doxorubicin to doxorubicinol, which is associated with a decreased risk of cardiotoxicity after doxorubicin administration.
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