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Tamoxifen has been used for the systemic treatment of patients with breast cancer for nearly three decades.

The recent results of a functional screen for breast cancer antiestrogen resistance ( Furthermore, high levels of BCAR1/p130Cas protein in ER-positive primary breast tumours are associated with intrinsic resistance to tamoxifen treatment.

Gefitinib pretreatment blocked receptor cross-talk, reestablished corepressor complexes with tamoxifen-bound ER on target gene promoters, eliminated tamoxifen's agonist effects, and restored its antitumor activity both The binding of estrogen to the estrogen receptor (ER) induces receptor phosphorylation, alters its conformation, triggers receptor dimerization, and facilitates binding of the receptor complex to the promoter region of target genes to activate transcription .

The conformation of estrogen-bound ER favors the recruitment of coactivators that augment transcriptional activity.

tamoxifen resistance in breast cancer elucidating mechanisms-62tamoxifen resistance in breast cancer elucidating mechanisms-26tamoxifen resistance in breast cancer elucidating mechanisms-7tamoxifen resistance in breast cancer elucidating mechanisms-30

Evidence was presented showing that the nature of tamoxifen itself may be the problem, as it has both estrogen-agonist and -antagonist properties. Although carefully collected, accuracy cannot be guaranteed. Differing provisions from the publisher's actual policy or licence agreement may be applicable.By contrast, the ER conformation induced by binding of the selective estrogen receptor modulator (SERM) tamoxifen favors the recruitment of corepressors that inhibit transcriptional activity.Tamoxifen has different partial agonist–antagonist activities in different tissues, however, and the differences may be related in part to the milieu of ER coactivators and corepressors in these tissues .The anti-oestrogen tamoxifen is the most commonly used treatment for patients with oestrogen-receptor (ER)-positive breast cancer.Although many patients benefit from tamoxifen in the adjuvant and metastatic settings, resistance is an important clinical problem. Over the last decade many advances have been made in our understanding of the biology of the ER which may help to explain how resistance to tamoxifen develops.




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