Breast cancer treatment failure in postmenopausal patients occurs when tumors progress, e.g., express a loss of differentiation, recur after primary therapy, become drug resistant, lose their response to estrogen as a growth factor, or metastasize. These properties emerge as the result of phenotypic diversity or heterogeneity and are expressed metabolically. The purpose of this study is to identify the 31p NMR metabolic changes in breast carcinoma in postmenopausal patients at the time of diagnosis of progression. The NMR data will also be correlated with expression of the neu/HER-2,,l H-ras, c-myc and int-2 oncogenes to determine if these genes play a role in the biochemical expression of a progressive malignant phenotype. These oncogene evaluations constitute a second research project to be conducted by Dr. Douglas E. Merkel. The 31p NMR studies will be performed on cancer tissue explants, perfused tissue extracts and continuous tumor cell lines, in addition to normal breast tissue. 13-C NMR spectroscopy using 13-C-labeled intermediates will provide information about metabolite patterns and flux through glycolysis, gluconeogenesis, and the Krebs cycle in estrogen-dependent tumors. The NMR methodology and the results of this research will potentially add to improved clinical accuracy of prognosis in gauging risks of tumor progression. This work may also lay the foundation for development of better, more specific therapeutic approaches in treatment of breast cancer, based upon the metabolic strategies of the cancer cell.
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