Breast cancer has been a principal focus of research at the UT Health Science Center in San Antonio for more than 20 years. The concept of translational research, bringing new laboratory findings quickly to clinical application to improve the treatment, quality of life, and survival of breast cancer patients, has been an integral part of this research since the beginning. For instance, our laboratory discovery of the heat shock protein hsp27 in breast cancer cell lines was quickly translated into the clinical finding that high levels of this and other hsp's in the primary tumor predict early recurrence of node-negative breast cancer. The same extensive tumor bank and database with long-term clinical follow-up which made this rapid translation possible has also permitted definitive prognostic studies on many other important factors, while basic cell and molecular biology research with the potential for early clinical implications is also ongoing. Now, this is SPORE application, we propose the further development of our translational breast cancer research emphasis, in several directions. (1) Our basic studies of tamoxifen resistance will now be translated into preclinical and clinical studies of new agents designed to overcome this resistance. (2) Our discovery of the prognostic significance of heat shock proteins led to our preliminary laboratory studies of their effect on drug resistance, which will be extended into clinical studies of their use as markers of resistance to specific chemotherapeutic regimens and the possibility of reversing resistance. (3) Our ongoing study of marker antigens such as oncogene proteins, invasive enzymes, and proliferation markers in evolutionary stages of premalignant breast lesions will provide surrogate endpoints in a new clinical trial treating potentially premalignant disease with agents such as tamoxifen. (4) A companion study will focus on the molecular genetics of the stages of premalignant breast disease, and on specific losses of heterozygosity which might mark lesions most likely to progress to malignancy. (5) Our studies of growth factor interactions on the EGF receptor in breast cancer as well as our laboratory and clinical experience with antibody-toxin conjugates will translate into pre-clinical and clinical trials of a new EGF-toxin fusion product targeting EGFR-expressing breast cancer cells. This will be only the second ligand fusion toxin to enter clinical trial. (6) Our long experience with both tumor and data collection in the San Antonio Breast Tumor Bank will be made available to other investigators immediately in a new National Breast Cancer Tissue Resource. (7) We will also develop a Familial Breast Cancer Resource, already initiated, focusing in particular on the large and highly localized Hispanic families in our region. (8) At least four developmental studies which could lead to early clinical application will also be undertaken at any one time; examples include analyzing DNA histograms for their prognostic implications in new ways, optimizing delivery of intact RB genes to cells where this tumor suppressor has been lost, and reversing clinical chemotherapeutic drug resistance with the tamoxifen analog toremifene. (9) One senior and two junior fellowships will be awarded each year for research work on specifically translational projects in breast cancer, to encourage development of focused research careers in this area. (10) Finally, we will offer the San Antonio Breast Cancer symposium, the largest annual international meeting specifically on breast cancer, as an appropriate and nearly ideal venue for the annual meeting of all breast cancer SPORE investigators.
Showing the most recent 10 out of 306 publications
