- Paper Report
- Open Access
GW5638: a new antiestrogen
- Fatima Cardoso1
© Biomed Central Ltd 2001
- Received: 13 September 2001
- Accepted: 13 September 2001
- Published: 1 December 2001
- Antiestrogen, breast cancer, GW5638, tamoxifen resistance
Approximately two-thirds of breast tumors are ER-positive (ER+), and therefore suitable for some type of endocrine therapy. Tamoxifen has been the standard hormonal therapy for the last 30 years. Nevertheless, less than two-thirds of ER+ tumors respond to tamoxifen, and eventually the majority of advanced tumors develop resistance to the drug. Even when the new hormonal agents are used, sublines of resistant cells may develop. Clearly, no single endocrine therapy will be enough to treat all ER+ breast cancer patients and new agents are needed. The authors tested GW5638 for potential activity against breast cancer.
When MCF-7 xenografts were treated with either tamoxifen or GW5638, different conformational changes were induced in the ER thereby exposing different surface peptides. These drugs therefore work by distinct mechanisms. Most importantly, tumoristatic doses of GW5638 inhibited growth of tamoxifen-resistant xenografts, both in the presence and in the absence of tamoxifen, as well as in ovary-intact animals (estradiol presence). These results suggest that GW5638 may be clinically useful for the treatment of both tamoxifen-naive and tamoxifen-resistant ER+ tumors.
Phage affinity selection; phase ELISA; cell culture and transient transfection; animal models; MCF-7 and MCF-7DU/TAM (tamoxifen-resistant) xenografts; statistical analysis performed with ANOVA, Kruskal-Wallis and multiple comparison tests