What is the mechanism of action of tamoxifen in breast cancer and in non cancerous tissues?
The mechanism of action of tamoxifen is complex. Clearly, its principal mechanism of action is mediated by its binding to the estrogen receptor and the blocking of the proliferative actions of estrogen on mammary epithelium.
What causes tamoxifen resistance?
The tamoxifen resistance is caused by estrogen via promoting Bcl-2: Bax ratio by estrogen. Besides, HER-2 overexpression increases the anti-apoptotic Bcl-2 and BclxL proteins which leads to the reduction in tamoxifen induced apoptosis and boosts tamoxifen resistance .
Can cancer become resistant to tamoxifen?
Estrogen-receptor positive (ER+) breast cancer tumors are frequently treated with the drug tamoxifen, which blocks the hormone’s effect on the tumor. However, many tumors eventually become resistant to tamoxifen, allowing cancer to recur or metastasize.
What is tamoxifen used to treat?
It can be used to treat women with breast cancer who have or have not gone through menopause. Tamoxifen can be used in several ways: In women at high risk of breast cancer, tamoxifen can be used to help lower the risk of developing breast cancer.
What type of breast cancer is treated with tamoxifen?
In women at high risk of breast cancer, tamoxifen can be used to help lower the risk of developing breast cancer. For women who have been treated with breast-conserving surgery for ductal carcinoma in situ (DCIS) that is hormone receptor-positive, taking tamoxifen for 5 years lowers the chance of the DCIS coming back.
What drugs should not be taken with tamoxifen?
The medications under the heading “Not Inhibitors” do not block the CYP2D6 enzyme and will not interfere with tamoxifen treatment….Medicines to avoid while taking tamoxifen.
How common is tamoxifen resistance?
Tamoxifen treatment of estrogen receptor (ER)-positive breast cancer reduces mortality by 31%. However, over half of advanced ER-positive breast cancers are intrinsically resistant to tamoxifen and about 40% will acquire the resistance during the treatment.
Is tamoxifen really effective?
Tamoxifen is a highly effective breast cancer treatment. It may significantly lower your risk of breast cancer recurrence or invasive breast cancer. People who are at high risk for breast cancer may take tamoxifen to reduce their chances of getting the disease.
How is tamoxifen resistance in breast cancer regulated?
Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor, and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1.
How are genes down regulated by tamoxifen treatment?
Recent data using microarray analysis to assess gene expression in the MCF7 cell line, suggests that the majority (70%) of oestrogen-regulated genes are down-regulated by treatment with oestradiol ( Frasor et al. 2003 ). Those genes down-regulated were shown to be transcriptional repressors, anti-proliferative and pro-apoptotic genes.
How is GREB1 and ERα related to tamoxifen?
Considering that GREB1 is a critical regulatory protein of ERα activity and that it exerts differential biological functions in tamoxifen-sensitive versus tamoxifen-refractory cells, GREB1–ERα axis may play a pivotal role in determining cell fate in response to the antiestrogen treatment.
Which is the strongest interactor of estrogen in breast cancer?
Recently, growth regulation by estrogen in breast cancer 1 (GREB1) was identified as the strongest interactor of estrogen-liganded, but not tamoxifen-liganded ERα ( 2 ).