What is the mechanism of action of tamoxifen?
Tamoxifen (TAM) is known to have a dual mechanism of action: (1) to compete with 17β-estradiol (E2) at the receptor site and to block the promotional role of E2 in breast cancer; and (2) to bind DNA after metabolic activation and to initiate carcinogenesis.
What is the mechanism of action of the drug tamoxifen in the treatment of breast cancer?
Tamoxifen blocks estrogen from connecting to the cancer cells and telling them to grow and divide. While tamoxifen acts like an anti-estrogen in breast cells, it acts like an estrogen in other tissues, like the uterus and the bones. Because of this, it is called a selective estrogen receptor modulator (SERM).
How does tamoxifen work gene expression?
The study found that tamoxifen regulates hTERT gene expression in a cell type-specific manner. Tamoxifen exerted an estrogen-antagonistic effect and inhibited E2-induced hTERT activation in breast cancer cells.
How does tamoxifen work Pubmed?
Tamoxifen is a selective estrogen modulator that competes with the estrogen for estrogen receptor and displaces estrogen and thereby inhibits estrogen function in breast tissue rather than suppression of circulating estrogen levels (Figure 1).
How is tamoxifen excreted from the body?
Tamoxifen is extensively metabolized after oral administration. Studies in women receiving 20 mg of 14C tamoxifen have shown that approximately 65% of the administered dose is excreted from the body over a period of 2 weeks with fecal excretion the primary route of elimination.
What are the indications of tamoxifen?
Indications for: Tamoxifen Axillary node-negative breast cancer in women after surgery + irradiation. Reduction in risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) after surgery + radiation. Reduction in breast cancer incidence in high-risk women.
Is tamoxifen an agonist or antagonist?
Tamoxifen is both an antagonist and an agonist of the estrogen receptor. However, a molecular explanation exists for this apparent paradox. The dual action is a function of the estrogen receptor complex present in a particular cell or tissue.
How is tamoxifen excreted?
What are the metabolites of tamoxifen?
Tamoxifen is metabolized via CYP2D6 into endoxifen (4-OH-N-desmethyl-tamoxifen), its primary active metabolite. Multiple investigations have identified genetic variants of CYP2D6 that can affect its activity, which in turn affects the metabolism of tamoxifen.