TY - JOUR
T1 - Pharmacogenetics of Drug Metabolism
T2 - The Role of Gene Polymorphism in the Regulation of Doxorubicin Safety and Efficacy
AU - Bagdasaryan, Alina A.
AU - Chubarev, Vladimir N.
AU - Smolyarchuk, Elena A.
AU - Drozdov, Vladimir N.
AU - Krasnyuk, Ivan I.
AU - Liu, Junqi
AU - Fan, Ruitai
AU - Tse, Edmund
AU - Shikh, Evgenia V.
AU - Sukocheva, Olga A.
PY - 2022/11/4
Y1 - 2022/11/4
N2 - 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.
AB - 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.
KW - Breast cancer
KW - doxorubicin
KW - drug toxicity
KW - pharmacogenetics
KW - gene polymorphism
KW - cytochrome P450
KW - MDRI protein
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85141707589&partnerID=8YFLogxK
U2 - 10.3390/cancers14215436
DO - 10.3390/cancers14215436
M3 - Review article
AN - SCOPUS:85141707589
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 21
M1 - 5436
ER -
