Question

Tamoxifen, which has a structure similar to the hormone estrogen, is the most used drug to treat breast cancer. Addition of tamoxifen to cultures of uterine carcinoma cells leads to decrease in several transcription activators known to induce proliferation. What is a possible target of this drug? Explain the molecular mechanism of its action. Be specific.

Answer 1

Estrogen receptors are the most important cell target in view of both control of carcinogenesis and inhibition of tumour cell growth. Results of studies over many years of tamoxifen treatment of patients with ER-positive breast cancer are an excellent confirmation of this finding.

Key mediators of signal pathways and cellular receptor proteins targeted by tamoxifen, as it demonstrates that tamoxifen is a unique polyvalent targeted drug. Tamoxifen action on targets activates or inhibits most important biological processes that controls tumour growth and known to induce proliferation that response to chemotherapy. Outcomes of tamoxifen action on cells are prognostically good from the point of view of both tumor growth/ metastasis inhibition and tumor response to drug therapy. So assessment of tamoxifen cellular targets other than Estrogen receptors will help enlarge indications of adjuvant tamoxifen therapy not only in breast cancer but also in tumors in other sites.

Tamoxifen acts as an agonist for GPR30 to stimulate cell proliferation and growth . Understanding the molecular mechanism of tamoxifen promoted is essential to identify strategies to lower the risk of developing breast cancer patients being treated with tamoxifen. Tamoxifen induces the recruitment of co-repressors nuclear receptors co-repressors and silencing mediators for retinoid to ER target promoters. However, tamoxifen recruits SRC-1 amplified in AIB1 and CBP rather than co-repressors to ER target gene. The modulation of estrogenic pathways is important in mediating the cell proliferation promoting effects of tamoxifen. In addition, tamoxifen known to regulate gene targets that are independent of estrogen. The proliferation index , determined by measuring the proliferation marker Ki67 is higher in the lesions of tamoxifen users compared with those of non-users.