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Pathway Description
Tamoxifen Action Pathway
Homo sapiens
Drug Action Pathway
Tamoxifen is a selective estrogen modulator (SERM) used in the treatment of estrogen-sensitive breast cancer. Tamoxifen itself only has weak anti-estrogen effects and must be converted into more active metabolites to have therapeutic activity. Metabolism takes place in the liver and is carried out primarily by cytochrome P450 enzymes. Tamoxifen is hydroxylated by CYP2D6 and demethylated by CYP3A4 and CYP3A5, producing the active metabolites 4-hydroxytamoxifen and endoxifen. These metabolites inhibit estrogen binding to estrogen receptors in breast cancer cells, which in turn inhibit tumour growth.
References
Tamoxifen Pathway References
Brauch H, Murdter TE, Eichelbaum M, Schwab M: Pharmacogenomics of tamoxifen therapy. Clin Chem. 2009 Oct;55(10):1770-82. doi: 10.1373/clinchem.2008.121756. Epub 2009 Jul 2.
Pubmed: 19574470
Hoskins JM, Carey LA, McLeod HL: CYP2D6 and tamoxifen: DNA matters in breast cancer. Nat Rev Cancer. 2009 Aug;9(8):576-86. doi: 10.1038/nrc2683.
Pubmed: 19629072
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