The Identification of Estrogen Responsive Genes in the Hypothalamic-Pituitary Axis
Abstract
Tamoxifen, the most widely used adjuvant therapy for the treatment of estrogen receptor positive breast cancer, has been shown to inhibit the growth of MCF-7 breast cancer cells in athymic mice. However, in both the animal model and clinical selling, therapeutic utility is limited by the development of resistance to the drug. Our goal is to determine whether GW5638, a structurally similar yet mechanistically distinct compound, can inhibit the growth of tamoxifen refractory tumors. We demonstrated that GW5638 was able to inhibit the growth of estrogen-dependent MCF-7 tumors in athymic mice. We subsequently developed tumor variants which are no longer sensitive to the inhibitory effects of tamoxifen; the tumors in fact require tamoxifen, but not estrogen, for growth. The resistant tumors were implanted into athymic mice treated with tamoxifen, GW5638, or both drugs. Two important findings emerged from these studies: 1) GW5638 alone cannot support the growth of tamoxifen-dependent tumors, and 2) GW5638 inhibits the growth of these tumors in the presence of tamoxifen. We conclude that tamoxifen-refractory tumors are not cross-resistant to GW5638, despite the structural similarities of the two compounds. These data support the therapeutic potential of GW5638 for the treatment of tamoxifen-resistant breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADB248567
Entities
People
- Caroline E. Connor
Organizations
- Duke University Hospital