Tamoxifen action mechanisms

Wiseman H, Quinn P, Halliwell B (1993) Tamoxifen and related compounds decrease membrane fluidity in liposomes mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions FEBS Lett 330( 1) 53—56... 

Wiseman H (1994) Tamoxifen new membrane-mediated mechanisms of action and therapeutic advances. Trends Pharmacol Sci 15(3) 83—89... 

Pure antiestrogens, which act by different mechanisms of action, probably are not affected by the mechanisms of tamoxifen resistance. As a result, those compounds might be a good choice as second-line hormonotherapy of breast cancer after failure of tamoxifen treatment, as has been reported in clinical... 

The evidence that tamoxifen was able to exert estrogenic effects on several tissues like the bone (Love et al. 1992) opened the door to the concept of SERMs, which is explained in detail in Chaps. 2 and 3 of this book. The mechanisms of action of these substances on ERs is explained in detail in Chap. 3. However, it is pertinent to comment on some special aspects of its action on mammary cancer cells. IGF-1 is a key element in growth control of malignant breast cells through endocrine and paracrine pathways. Tamoxifen and its active metabolite are able to inhibit IGF-l-stimulated growth (Jordan... 

These clinical observations demonstrate that the effect of tamoxifen and other SERMs on the endometrium needs to be studied in depth in order to offer objective evidence-based information on these compounds to our patients. This chapter provides a summary of the information available on the mechanism of action and on the clinical data of SERMs on the endometrium. 

Black LJ, Goode RL (1981) Evidence for biological action of the antiestrogens LY117018 and tamoxifen by different mechanisms. Endocrinology 109(3) 987-989... 

Wiseman H. Dietary phytoestrogens, oestrogens and tamoxifen mechanisms of action in modulation of breast cancer risk and in heart disease prevention. In Biomolecular Free Radical Toxicity Causes and Prevention (H Wiseman, P Goldfarb, TJ Ridgway, A Wiseman, editors) John Wiley, Chichester, pp. 170-208, 2000. 

Malkin A, Meakin JW. Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma. Cancer Res 1986 46(6) 3152-6. 

Of these active metabolites, endoxifen is suggested to be the primary active metabolite responsible for the majority of tamoxifen clinical efficacy, as endoxifen plasma concentrations are about five to tenfold higher than those of 4-hydroxy-tamoxifen [11, 165], Endoxifen may have additional mechanisms of action than 4-hydroxy-tamoxifen by targeting Era for degradation by proteasome [166] and through the promotion of ERa/ERf) heterodimerization, blocking ERa transcriptional activity [167],... 

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