Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy.
Article Details
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Cronin-Fenton DP, Damkier P, Lash TL
Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy.
Future Oncol. 2014 Jan;10(1):107-22. doi: 10.2217/fon.13.168.
- PubMed ID
- 24328412 [ View in PubMed]
- Abstract
Tamoxifen reduces the rate of breast cancer recurrence by approximately a half. Tamoxifen is metabolized to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen is a substrate for ATP-binding cassette transporter proteins. We review tamoxifen's clinical pharmacology and use meta-analyses to evaluate the clinical epidemiology studies conducted to date on the association between CYP2D6 inhibition and tamoxifen effectiveness. Our findings indicate that the effect of both drug-induced and/or gene-induced inhibition of CYP2D6 activity is likely to be null or small, or at most moderate in subjects carrying two reduced function alleles. Future research should examine the effect of polymorphisms in genes encoding enzymes in tamoxifen's complete metabolic pathway, should comprehensively evaluate other biomarkers that affect tamoxifen effectiveness, such as the transport enzymes, and focus on subgroups of patients, such as premenopausal breast cancer patients, for whom tamoxifen is the only guideline endocrine therapy.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Tamoxifen Cytochrome P450 1A2 Protein Humans UnknownSubstrateDetails Tamoxifen Estrogen sulfotransferase Protein Humans UnknownSubstrateDetails Tamoxifen UDP-glucuronosyltransferase 2B17 Protein Humans UnknownSubstrateDetails Tamoxifen UDP-glucuronosyltransferase 2B7 Protein Humans UnknownSubstrateDetails - Drug Reactions
Reaction Details Details
