This renewal application of the Mayo Clinic Breast Cancer SPORE is being submitted with full support of Mayo Clinic Cancer Center (MCCC) and Mayo Foundation to continue translational research directed at reducing the burden and mortality from breast cancer. The science of the SPORE includes four translational research projects: Project 1: """"""""Risk assessment for carriers of Variants of Uncertain Significance (VUS) in the BRCA1 and BRCA2 breast cancer predisposition genes"""""""" will continue this clinically important and highly translational research that addresses a clear unmet need of many woman to determine their personal risk of breast cancer when tested for BRCA 1/2 and given the result of a VUS. Project 2: """"""""Endoxifen as a novel hormonal therapy for breast cancer"""""""" is based on Mayo investigator derived preclinical data indicating that endoxifen has superior anti-tumor activity than tamoxifen. These data led NCI to develop clinical grade endoxifen, which will be used in a first-in-human phase I clinical trial in this SPORE project. Project 3: """"""""Regulation of hormone resistant breast cancer by IGF and insulin system signaling"""""""" focuses on a novel approach to dealing with resistance to hormonal therapy by focusing on the role of the insulin receptor A isoform as a (co-)mediator of insulin growth factor pathway signaling. Additional pre-clinical studies are planned and complete IGF and estrogen receptor blockade will be examined in a phase II clinical trial that is notable for intensive biospecimen acquisition, including biopsies, for translational studies in the Co-Leaders'labs. Project 4: """"""""Improving breast cancer risk prediction for women with benign breast disease"""""""" addresses the highly important need for better prediction of risk in the individual patient utilizing features present in the patient's benign breast tissue (BBD). This project will identify novel biomarkers and build a risk prediction model using the large Mayo BBD Cohort with subsequent validation in a SPORE-SPORE collaboration. These research projects are supported by three highly interactive cores: Core A: Administrative Core, Core B;. Biospecimen and Pathology Core, and Core C: Biostatistics and Patient Registry Core. A Developmental Research Program will continue to identify and develop research projects that hold the greatest promise to advance to full SPORE projects, and a Career Development Program will continue to identify and support faculty investigators in breast cancer translational research that have the greatest potential to become future SPORE leaders. The investigators, core facilities, and the research programs in the SPORE are all integrated into the MCCC and, collectively, will advance knowledge and translate findings into the clinic for the benefit of women with, or at risk for, breast cancer.
Breast cancer is the most common cancer in women and the Mayo Clinic Breast Cancer SPORE proposes to continue to conduct research that through translation will reduce morbidity and mortality from the disease. This will be accomplished through two projects addressing risk of developing breast cancer and two projects directed at improving therapy of breast cancer.
|Yu, Jia; Qin, Bo; Moyer, Ann M et al. (2018) DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine. J Clin Invest 128:2376-2388|
|Kannan, Nagarajan; Eaves, Connie J (2018) Macrophages stimulate mammary stem cells. Science 360:1401-1402|
|Guidugli, Lucia; Shimelis, Hermela; Masica, David L et al. (2018) Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches. Am J Hum Genet 102:233-248|
|Kurmi, Kiran; Hitosugi, Sadae; Wiese, Elizabeth K et al. (2018) Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity. Cell Rep 22:1365-1373|
|Goetz, Matthew P; Sangkuhl, Katrin; Guchelaar, Henk-Jan et al. (2018) Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Clin Pharmacol Ther 103:770-777|
|Baheti, Saurabh; Tang, Xiaojia; O'Brien, Daniel R et al. (2018) HGT-ID: an efficient and sensitive workflow to detect human-viral insertion sites using next-generation sequencing data. BMC Bioinformatics 19:271|
|Hart, Steven N; Hoskin, Tanya; Shimelis, Hermela et al. (2018) Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models. Genet Med :|
|Ho, Ming-Fen; Correia, Cristina; Ingle, James N et al. (2018) Ketamine and ketamine metabolites as novel estrogen receptor ligands: Induction of cytochrome P450 and AMPA glutamate receptor gene expression. Biochem Pharmacol 152:279-292|
|Yang, Yuzhe; Chan, Jie Ying; Temiz, Nuri A et al. (2018) Insulin Receptor Substrate Suppression by the Tyrphostin NT157 Inhibits Responses to Insulin-Like Growth Factor-I and Insulin in Breast Cancer Cells. Horm Cancer 9:371-382|
|Ingle, James N; Kalari, Krishna R; Wickerham, Donald Lawrence et al. (2018) Germline genome-wide association studies in women receiving neoadjuvant chemotherapy with or without bevacizumab. Pharmacogenet Genomics 28:147-152|
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