The overall goal ofthis proposal is to build a multi-scale modeling platform for investigation ofthe breast cancer, with special emphasis on the roles ofthe tumor-initiating cells (TIC). This modeling platform will mainly consist of two closely related components: biological experiments and mathematical computational modeling. For the experiment component, we seek to use newly developed experimental and imaging methodologies to identify, localize, purify and characterize TIC. Further experiments will be designed to discover the spatial localization and movement, and specific changes in gene expression and cellular signaling of breast cancer TIC. Combined functional genomics and data mining strategies will allow us to characterize novel growth regulators. Further, our combined experimental and systems biology approach will allow us to evaluate responses to experimental therapeutics that may inhibit or kill TIC specifically in a manner not possible before. For the mathematical modeling component, we will develop bioinformatics and bio-imaging models to integrate and analyze the data generated from biological experiments, and make use ofthe information obtained from data analysis, biological knowledge to build in silico models to model TIC behavior, cancer cell apoptosis, cell migration, cycle and drug treatment response. Besides providing a basic framework for understanding the mechanism underlying breast cancer stem cell evolution, the models can also give birth to hypotheses or experimental design. More important, these models will allow one to predict the biological state under investigation and predict how the natural process will behave in various circumstances. Iterative feedback between these two components will refine our proposed platform further. The ultimate goal is an integrated modeling platform of breast cancer biology that can mimic in vivo processes faithfully enough to serve as a h5TDOthesis-generation and screening tool, and in the distant future, as a tool for evaluating clinical procedures and their expected outcomes.
This project will be a substantial contribution to the public health by understanding the mechanism of cancer initial cells or cancer stem cells. More importantly, the completion ofthis screening project will help to answer some critical questions related to breast caner. Such understanding will in turn advance our knowledge in tumor biology and open up the possibility of novel treatments in the future.
|Neelakantan, Deepika; Zhou, Hengbo; Oliphant, Michael U J et al. (2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773|
|Chen, Suyun; Ibrahim, Nuhad K; Yan, Yuanqing et al. (2017) Complete Metabolic Response on Interim 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Long-Term Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy. Oncologist 22:526-534|
|Liang, Diana H; Choi, Dong Soon; Ensor, Joe E et al. (2016) The autophagy inhibitor chloroquine targets cancer stem cells in triple negative breast cancer by inducing mitochondrial damage and impairing DNA break repair. Cancer Lett 376:249-58|
|Dong, J; Zhao, W; Shi, A et al. (2016) The PR status of the originating cell of ER/PR-negative mouse mammary tumors. Oncogene 35:4149-54|
|Dobrolecki, Lacey E; Airhart, Susie D; Alferez, Denis G et al. (2016) Patient-derived xenograft (PDX) models in basic and translational breast cancer research. Cancer Metastasis Rev 35:547-573|
|Tanei, Tomonori; Choi, Dong Soon; Rodriguez, Angel A et al. (2016) Antitumor activity of Cetuximab in combination with Ixabepilone on triple negative breast cancer stem cells. Breast Cancer Res 18:6|
|Yeung, Tsz-Lun; Leung, Cecilia S; Li, Fuhai et al. (2016) Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment. Biomolecules 6:3|
|Hein, S M; Haricharan, S; Johnston, A N et al. (2016) Luminal epithelial cells within the mammary gland can produce basal cells upon oncogenic stress. Oncogene 35:1461-7|
|Park, Jun Hyoung; Vithayathil, Sajna; Kumar, Santosh et al. (2016) Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer. Cell Rep 14:2154-2165|
|Zhao, Zhen; Zhu, Xiaoping; Cui, Kemi et al. (2016) In Vivo Visualization and Characterization of Epithelial-Mesenchymal Transition in Breast Tumors. Cancer Res 76:2094-2104|
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