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Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management

There is wide individual variability in the pharmacokinetics, pharmacodynamics, and tolerance to anticancer drugs within the same ethnic group and even greater variability among different ethnicities. Pharmacogenomics (PG) has the potential to provide personalized therapy based on individual genetic...

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Detalles Bibliográficos
Autores principales: Rofaiel, Sarah, Muo, Esther N, Mousa, Shaker A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513214/
https://www.ncbi.nlm.nih.gov/pubmed/23226048
http://dx.doi.org/10.2147/PGPM.S10789
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author Rofaiel, Sarah
Muo, Esther N
Mousa, Shaker A
author_facet Rofaiel, Sarah
Muo, Esther N
Mousa, Shaker A
author_sort Rofaiel, Sarah
collection PubMed
description There is wide individual variability in the pharmacokinetics, pharmacodynamics, and tolerance to anticancer drugs within the same ethnic group and even greater variability among different ethnicities. Pharmacogenomics (PG) has the potential to provide personalized therapy based on individual genetic variability in an effort to maximize efficacy and reduce adverse effects. The benefits of PG include improved therapeutic index, improved dose regimen, and selection of optimal types of drug for an individual or set of individuals. Advanced or metastatic breast cancer is typically treated with single or multiple combinations of chemotherapy regimens including anthracyclines, taxanes, antimetabolites, alkylating agents, platinum drugs, vinca alkaloids, and others. In this review, the PG of breast cancer therapeutics, including tamoxifen, which is the most widely used therapeutic for the treatment of hormone-dependent breast cancer, is reviewed. The pharmacological activity of tamoxifen depends on its conversion by cytochrome P450 2D6 (CYP2D6) to its abundant active metabolite, endoxifen. Patients with reduced CYP2D6 activity, as a result of either their genotype or induction by the coadministration of other drugs that inhibit CYP2D6 function, produce little endoxifen and hence derive limited therapeutic benefit from tamoxifen; the same can be said about the different classes of therapeutics in breast cancer. PG studies of breast cancer therapeutics should provide patients with breast cancer with optimal and personalized therapy.
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spelling pubmed-35132142012-12-05 Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management Rofaiel, Sarah Muo, Esther N Mousa, Shaker A Pharmgenomics Pers Med Review There is wide individual variability in the pharmacokinetics, pharmacodynamics, and tolerance to anticancer drugs within the same ethnic group and even greater variability among different ethnicities. Pharmacogenomics (PG) has the potential to provide personalized therapy based on individual genetic variability in an effort to maximize efficacy and reduce adverse effects. The benefits of PG include improved therapeutic index, improved dose regimen, and selection of optimal types of drug for an individual or set of individuals. Advanced or metastatic breast cancer is typically treated with single or multiple combinations of chemotherapy regimens including anthracyclines, taxanes, antimetabolites, alkylating agents, platinum drugs, vinca alkaloids, and others. In this review, the PG of breast cancer therapeutics, including tamoxifen, which is the most widely used therapeutic for the treatment of hormone-dependent breast cancer, is reviewed. The pharmacological activity of tamoxifen depends on its conversion by cytochrome P450 2D6 (CYP2D6) to its abundant active metabolite, endoxifen. Patients with reduced CYP2D6 activity, as a result of either their genotype or induction by the coadministration of other drugs that inhibit CYP2D6 function, produce little endoxifen and hence derive limited therapeutic benefit from tamoxifen; the same can be said about the different classes of therapeutics in breast cancer. PG studies of breast cancer therapeutics should provide patients with breast cancer with optimal and personalized therapy. Dove Medical Press 2010-09-17 /pmc/articles/PMC3513214/ /pubmed/23226048 http://dx.doi.org/10.2147/PGPM.S10789 Text en © 2010 Rofaiel et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
Rofaiel, Sarah
Muo, Esther N
Mousa, Shaker A
Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management
title Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management
title_full Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management
title_fullStr Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management
title_full_unstemmed Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management
title_short Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management
title_sort pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513214/
https://www.ncbi.nlm.nih.gov/pubmed/23226048
http://dx.doi.org/10.2147/PGPM.S10789
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