This is the second competing renewal application of the Vanderbilt-lngram Cancer Center (VICC) Breast Cancer SPORE Grant. We have made significant progress in our previous funding cycle, have established productive collaborations with other Breast Cancer SPOREs and national and international groups, and have firmly established a true multidisciplinary program which we believe will be increasingly productive in the years to come. Our overall goal continues to be to conduct multidisciplinary, mechanism-based, translational research of the highest possible impact that will contribute meaningfully to measurable progress in breast cancer. To this end and after internal and external review, we now propose four bidirectional translational projects addressing basic, clinical and population research questions in human breast cancer. Two of these are continuations and two are new projects. The application also includes five shared cores resources, and developmental research and career development programs. Project 1: Inhibition of PI3 kinase as a strategy to abrogate antiestrogen resistance in breast cancer Project 2: Strategies to improve outcomes for triple negative breast cancer patients involving subtype-specific targeted therapies and genomic discovery Project 3: Mcl-1 inhibitors for the treatment of breast cancer Project 4: The obesity-metabolic biomarker axis and breast cancer risk Core Resources. To support the research aims in the translational research projects, we propose five shared Core Resources. Each of these Cores supports at least 2 projects in this competing renewal. They are Administration &Outreach, Pathology &Tissue Informatics (formerly called Tissue), Clinical, Biostatistics, and Imaging Cores. We should emphasize that these Cores do not duplicate pre-existing resources available at VICC or VUMC. The proposed Projects will require additional personnel and funded effort over that already maximally utilized in equivalent institutional Core Resources.

Public Health Relevance

These four projects will transform how we diagnose and treat individuals with breast cancer and deepen our understanding of the pathobiology of mammary neoplasia. A patient advocate is an integral member of each project to help ensure that our translational goals are being met.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Study Section
Special Emphasis Panel (ZCA1-RPRB-0 (M1))
Program Officer
Kuzmin, Igor A
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Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
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Santos Guasch, Gabriela L; Beeler, J Scott; Marshall, Clayton B et al. (2018) p73 Is Required for Ovarian Follicle Development and Regulates a Gene Network Involved in Cell-to-Cell Adhesion. iScience 8:236-249
Croessmann, Sarah; Sheehan, Jonathan H; Lee, Kyung-Min et al. (2018) PIK3CA C2 Domain Deletions Hyperactivate Phosphoinositide 3-kinase (PI3K), Generate Oncogene Dependence, and Are Exquisitely Sensitive to PI3K? Inhibitors. Clin Cancer Res 24:1426-1435
Elion, David L; Cook, Rebecca S (2018) Harnessing RIG-I and intrinsic immunity in the tumor microenvironment for therapeutic cancer treatment. Oncotarget 9:29007-29017
Williams, Michelle M; Lee, Linus; Werfel, Thomas et al. (2018) Intrinsic apoptotic pathway activation increases response to anti-estrogens in luminal breast cancers. Cell Death Dis 9:21
Hyman, David M; Piha-Paul, Sarina A; Won, Helen et al. (2018) HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 554:189-194
Luo, Na; Nixon, Mellissa J; Gonzalez-Ericsson, Paula I et al. (2018) DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer. Nat Commun 9:248
Sudhan, Dhivya R; Schwarz, Luis J; Guerrero-Zotano, Angel et al. (2018) Extended Adjuvant Therapy with Neratinib Plus Fulvestrant Blocks ER/HER2 Crosstalk and Maintains Complete Responses of ER+/HER2+ Breast Cancers: Implications to the ExteNET Trial. Clin Cancer Res :
Werfel, Thomas A; Wang, Shan; Jackson, Meredith A et al. (2018) Selective mTORC2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and Survival. Cancer Res 78:1845-1858
Zhao, Shilin; Li, Chung-I; Guo, Yan et al. (2018) RnaSeqSampleSize: real data based sample size estimation for RNA sequencing. BMC Bioinformatics 19:191
Williams, Michelle M; Lee, Linus; Hicks, Donna J et al. (2017) Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade. Mol Cancer Res 15:259-268

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