Key result
Specific gene polymorphisms in cytochrome P450 and p-glycoproteins alter doxorubicin metabolism, impacting its efficacy and the risk of cardiotoxicity in breast cancer patients.
Why the study?
Cardiotoxicity is a major adverse reaction to doxorubicin in breast cancer therapy, and determining specific gene polymorphisms altering drug metabolism may improve safety and efficacy.
Do specific gene polymorphisms alter doxorubicin metabolism, safety, and efficacy in breast cancer patients?
Do specific gene polymorphisms alter doxorubicin metabolism, safety, and efficacy in breast cancer patients?
Genetic differences in doxorubicin metabolism pathways may enable personalized treatment to maximize efficacy and minimize cardiotoxicity in breast cancer patients.
May support pharmacogenetic screening before doxorubicin in breast cancer; leaves open whether testing improves outcomes.
Breast cancer (BC) is the prevailing malignancy and major cause of cancer-related death in females. Doxorubicin is a part of BC neoadjuvant and adjuvant chemotherapy regimens. The administration of anthracycline derivates, such as doxorubicin, may cause several side effects, including hematological disfunction, gastrointestinal toxicity, hepatotoxicity, nephrotoxicity, and cardiotoxicity. Cardiotoxicity is a major adverse reaction to anthracyclines, and it may vary depending on individual differences in doxorubicin pharmacokinetics. Determination of specific polymorphisms of genes that can alter doxorubicin metabolism was shown to reduce the risk of adverse reactions and improve the safety and efficacy of doxorubicin. Genes which encode cytochrome P450 enzymes (CYP3A4 and CYP2D6), p-glycoproteins (ATP-binding cassette (ABC) family members such as Multi-Drug Resistance 1 (MDR1) protein), and other detoxifying enzymes were shown to control the metabolism and pharmacokinetics of doxorubicin. The effectiveness of doxorubicin is defined by the polymorphism of cytochrome p450 and p-glycoprotein-encoding genes. This study critically discusses the latest data about the role of gene polymorphisms in the regulation of doxorubicin's anti-BC effects. The correlation of genetic differences with the efficacy and safety of doxorubicin may provide insights for the development of personalized medical treatment for BC patients.
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Bagdasaryan et al. (2022) conducted a review in Breast cancer. Gene polymorphisms was evaluated. Specific gene polymorphisms in cytochrome P450 and p-glycoproteins alter doxorubicin metabolism, impacting its efficacy and the risk of cardiotoxicity in breast cancer patients.
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