Fellowship to Identify New Mechanisms of Tamoxifen Resistance in Breast Cancer Patients
Annual rept. 15 Sep 1995-14 Sep 1996
TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
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The non-steroidal antiestrogen tamoxifen TAM has been used successfully in the treatment of tens of thousands of women with breast cancer, has been shown to increase both disease-free and overall survival in treated patients. Unfortunately, virtually all patients treated with TAM eventually develop resistant disease. The research funded by this fellowship is directed at increasing our understanding of the mechanisms leading to the development of tamoxifen resistance. Specific Aim 1 of this proposal has been completed and three altered estrogen receptors ERs have been identified from clinical samples, one of which exhibits a hormone-independent phenotype in transient assays. We are currently generating the necessary constructs or screening this ER variant for activity consistent with the development of hormone-independent growth in vivo Aim 2. We have also worked out the technical aspects of microdissection of archival and frozen clinical tumor samples to improve the use of differential display technologies to examine these samples for altered gene expression coincident with the phenotype of tamoxifen resistance Aims 3 and 4.
- Medicine and Medical Research