Four-Dimensional Heterogeneity of Fluid Phase Biopsies in Cancer (4DB-Center)

通过血流的癌症转移可以建模为在复杂流场中运动的不同质量、动量和物理性质的多个体（细胞）的流固相互作用问题。四维活检中心（4DB）利用基于物理的测量，数学建模和数值模拟来经验地表征实际的人类癌症患者样本，其目标是建立人类癌细胞行为的高度预测模型，这将从根本上改变我们目前对癌症转移机制的理解。广泛的实证测量和分析将对一组连贯的人类癌症患者样本进行。样本将包括原发肿瘤细胞、局部转移细胞和循环肿瘤细胞（ctc），这些细胞都来自同一患者。此外，第二组样本将由来自大量患者的ctc组成，按肿瘤类型和癌症分期分层。这些样本集将由三个独立的研究项目（rp）并行分析，产生相同现象的正交测量，并提供上皮性癌症在空间和时间维度上的变量和相关性。三个研究项目（RP）是：RP1细胞物理学，它决定了癌细胞的物理和机械特性；RP2拓扑，用于测量癌细胞的拓扑、形态和移动群策略；以及描述癌细胞基因组学和转录组学特征的RP3动力学。有了深度、广度和保真度的评估，测量将通过分析其他参数，包括标准的病理和临床患者信息来增强。这种广泛的数据合并，主要基于物理研究和数学理论，但根据策略性的患者抽样和临床信息，将通过先进的统计分析和数学建模进行处理，以实现对癌症扩散的高度预测模拟，这将彻底改变我们对转移的理解。4DB中心还将为新一代癌症物理学家提供信息、教育和培训；这一代人将运用物理学的力量来攻克癌症的难题。

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 empowered 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.