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. Under the first years of our SPORE, the same extensive breast tumor bank and database with long-term clinical follow-up which makes this rapid translation possible has become a national resource, while basic cell and molecular biology research with the potential for early clinical implications is also ongoing. In this SPORE renewal application, we propose the further development of our translational breast cancer research emphasis, in several directions. (1) Our basic studies of acquired tamoxifen resistance will test new mechanistic hypotheses, and strategies for overcoming this resistance in patients will be explored. (2) Our laboratory discoveries on the association of heat shock proteins with drug resistance will be translated into preclinical and clinical studies of methods of reversing this resistance. (3) Our ongoing study of marker antigens such as oncogene proteins, invasion enzymes, and proliferation markers in evolutionary stages of premalignant breast lesions will provide potential surrogate endpoints to be evaluated in a tamoxifen chemoprevention trial. (4) Having demonstrated both the clonal nature of premalignant lesions and their clonal progression to invasive breast cancer, we will seek genetic markers of risk to guide preventive treatment choices. (5) Our findings on tumor suppressor genes, and particularly on a newly discovered set of Rb- associated proteins, will be applied to define the role of a number of suppressor genes in clinical breast cancer, their use as biomarkers of prognosis and risk, and the possibilities of therapeutic reversal of their functional loss by adenovirus vectors carrying the normal genes. (6) Our long experience with both tumor and data collection in the San Antonio Breast Tumor Bank has been used to develop a SPORE National Breast Cancer Tissue Resource, which will continue to provide investigators all over the country with access to breast cancer specimens and associated clinical data. (7) Our Familial Breast Cancer Resource has already accrued over 200 breast cancer families, and will continue to identify families and collect blood samples for molecular genetic investigation, 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 be undertaken at any one time; current examples include preclinical study and a phase I clinical trial of IGF binding protein 1 as targeted therapy, development of comparative genomic hybridization (CGH) for paraffin-embedded archival breast tissue samples to screen cancers and premalignant lesions for genetic abnormalities, chemical modification of the drug camptothecin to stabilize the bioactive lactone form and enhance bioavailability, and development of a culturally sensitive decision instrument to investigate ways of overcoming the resistance of many Hispanic women to mammography screening. (9) Two career development awards will be made each year for research work on specifically translational projects in breast cancer, to encourage development of focused research careers in this area.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
7P50CA058183-08
Application #
2894983
Study Section
Special Emphasis Panel (SRC (27))
Program Officer
Kuzmin, Igor A
Project Start
1992-09-30
Project End
2002-11-30
Budget Start
1999-08-30
Budget End
2002-11-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Sukumaran, Sujita; Watanabe, Norihiro; Bajgain, Pradip et al. (2018) Enhancing the Potency and Specificity of Engineered T Cells for Cancer Treatment. Cancer Discov 8:972-987
Kaochar, Salma; Mitsiades, Nicholas (2018) A Novel Mechanism to Drive Castration-Resistant Prostate Cancer. Trends Endocrinol Metab 29:366-368
Bhat, Raksha R; Yadav, Puja; Sahay, Debashish et al. (2018) GPCRs profiling and identification of GPR110 as a potential new target in HER2+ breast cancer. Breast Cancer Res Treat 170:279-292
Guarducci, Cristina; Bonechi, Martina; Benelli, Matteo et al. (2018) Cyclin E1 and Rb modulation as common events at time of resistance to palbociclib in hormone receptor-positive breast cancer. NPJ Breast Cancer 4:38
Rimawi, Mothaffar F; De Angelis, Carmine; Contreras, Alejandro et al. (2018) Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer. Breast Cancer Res Treat 167:731-740
Hertz, D L; Kidwell, K M; Hilsenbeck, S G et al. (2017) CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study. Breast Cancer Res Treat 166:277-287
Yu, L; Liang, Y; Cao, X et al. (2017) Identification of MYST3 as a novel epigenetic activator of ER? frequently amplified in breast cancer. Oncogene 36:2910-2918
Guven, Adem; Villares, Gabriel J; Hilsenbeck, Susan G et al. (2017) Carbon nanotube capsules enhance the in vivo efficacy of cisplatin. Acta Biomater 58:466-478
Veeraraghavan, Jamunarani; De Angelis, Carmine; Reis-Filho, Jorge S et al. (2017) De-escalation of treatment in HER2-positive breast cancer: Determinants of response and mechanisms of resistance. Breast 34 Suppl 1:S19-S26
Xu, Xiaowei; De Angelis, Carmine; Burke, Kathleen A et al. (2017) HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2+ Breast Cancer. Clin Cancer Res 23:5123-5134

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