Cancer metastasis via the blood stream can be modeled as a problem of fluid-solid interaction with multiple bodies (cells) of different masses, momentum, and physical qualities, in motion, within a complex flow field. The Four Dimensional Biopsy Center (4DB) utilizes physics-based measurements, mathematical modeling and numerical simulation to empirically characterize actual human cancer patient samples, with a goal of establishing a highly predictive model of human cancer cell behavior that will fundamentally alter our current understanding of the mechanisms of cancer metastasis. Extensive empirical measurements and analyses will be performed on a coherent set of samples from human cancer patients. Samples will consist of cells from primary tumors, locoregional metastases, and circulating tumor cells (CTCs) over time, all collected from the same patient. Additionally, a second cohort of samples will consist of CTCs from a large set of patients, stratified by tumor type and cancer stage. These sample sets will be analyzed in parallel by three independent Research Projects (RPs), producing orthogonal measures of identical phenomena, and delivering the variables and the correlations on the space and time dimension of epithelial cancers. The three Research Projects (RP) are: RP1 Cytophysics, which determines the physical and mechanical properties of cancer cells;RP2 Topology, which measures the topology, morphology, and travel group strategies of cancer cells;and RP3 Dynomics, which characterizes the genomics and transcriptomics of cancer cells. With assessment of depth, breadth, and fidelity thus assured, the measurements will be empowerd by analyses of other parameters, including standard pathologic and clinical patient information. This extensive amalgamation of data, based primarily on physics investigations and mathematical theory, but informed by strategic patient sampling and clinical information, will be processed by advanced statistical analysis and mathematical modeling, to enable a highly predictive simulation of cancer spread that will revolutionize our understanding of metastasis. The 4DB Center will also serve to disseminate information, education, and training to a new generation of cancer physicists;a generation that will implement the power of physics to conquer the problems of cancer.

Public Health Relevance

Deaths due to metastatic cancer continue to mount. Despite decades of effort, this set of diseases continues to evade our best therapeutic efforts and our best biologic investigations. The Four Dimensional Biopsy Center (4DB) takes cancer research in a new direction by pinning the metastasizing cancer cell directly in the spotlight of powerful physics and mathematics based measurements and modeling.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-SRLB-9 (O1))
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Hanlon, Sean E
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Scripps Research Institute
La Jolla
United States
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West, Jeffrey; Newton, Paul K (2017) Chemotherapeutic Dose Scheduling Based on Tumor Growth Rates Provides a Case for Low-Dose Metronomic High-Entropy Therapies. Cancer Res 77:6717-6728
Kuhn, P; Keating, S M; Baxter, G T et al. (2017) Lessons Learned: Transfer of the High-Definition Circulating Tumor Cell Assay Platform to Development as a Commercialized Clinical Assay Platform. Clin Pharmacol Ther 102:777-785
Carlsson, Anders; Kuhn, Peter; Luttgen, Madelyn S et al. (2017) Paired High-Content Analysis of Prostate Cancer Cells in Bone Marrow and Blood Characterizes Increased Androgen Receptor Expression in Tumor Cell Clusters. Clin Cancer Res 23:1722-1732
West, Jeffrey; Hasnain, Zaki; Mason, Jeremy et al. (2016) The prisoner's dilemma as a cancer model. Converg Sci Phys Oncol 2:
Mitrugno, Annachiara; Tormoen, Garth W; Kuhn, Peter et al. (2016) The prothrombotic activity of cancer cells in the circulation. Blood Rev 30:11-9
Baker-Groberg, Sandra M; Phillips, Kevin G; Healy, Laura D et al. (2015) Critical behavior of subcellular density organization during neutrophil activation and migration. Cell Mol Bioeng 8:543-552
King, Michael R; Phillips, Kevin G; Mitrugno, Annachiara et al. (2015) A physical sciences network characterization of circulating tumor cell aggregate transport. Am J Physiol Cell Physiol 308:C792-802
Phillips, Kevin G; Lee, Angela M; Tormoen, Garth W et al. (2015) The thrombotic potential of circulating tumor microemboli: computational modeling of circulating tumor cell-induced coagulation. Am J Physiol Cell Physiol 308:C229-36
Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S et al. (2015) Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients. Phys Biol 12:016008
Phillips, Kevin G; Baker-Groberg, Sandra M; McCarty, Owen J T (2014) Quantitative optical microscopy: measurement of cellular biophysical features with a standard optical microscope. J Vis Exp :

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