The approach of targeted therapies has also evolved with a better understanding of cancer to achieve treatment outcomes accordingly. Cytochrome P450 (CYP) is one of these enzyme superfamilies that are of great pharmacogenomic interest due to its role in the biotransformation of several drugs, including anticancer drugs. These enzymes have the ability to metabolize procarcinogens and anticancer drugs, making them crucial in cancer etiology and treatment. Accordingly, the present study investigated the pharmacogenomics of Cytochrome P450 1A1, 3A4 & 3A5 genotypes in relation to treatment response (personalized medicine approach) in breast cancer cases receiving adjuvant tamoxifen.
Study participants included 300 women with breast cancer and a similar number of age-matched controls. CYP1A1, CYP3A4 & CYP3A5 genotypes were determined in genomic DNA by PCR-based RFLP. Follow-up was carried out to determine whether there was any correlation between the variants and treatment outcome. A Chi-square test and logistic regression models were used to investigate the association between genotype, use of concomitant CYP1A1, CYP3A4 & CYP3A5 inhibitors, and disease relapse rate.
CYP1A1, CYP3A4 & CYP3A5 variant alleles were significantly more frequent in the cases than in the controls. Moreover, this study showed that the presence of inactive CYP1A1, CYP3A4 & CYP3A5 resulted in a decrease in the metabolic activation of anticancer agents, lowering the risk of toxicity but worsening the therapeutic response. A deeper understanding of CYP1A1, CYP3A4 & CYP3A5 could lead to more effective targeted therapies for breast cancer.
In spite of advances in treatment for breast cancer, an effective treatment outcome with no side effects remains a challenge in Asian countries. The study of pharmacogenomics is expected to help in the standardization of chemotherapy drugs and improve treatment outcomes in cancer patients carrying CYP1A1, CYP3A4 & CYP3A5 variant genotypes (precision medicine/targeted therapies).
The authors.
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All authors have declared no conflicts of interest.