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

肿瘤通过血流转移可以被模拟为在复杂的流场中与具有不同质量、动量和物理性质的多个物体(细胞)进行流固相互作用的问题。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对实际的人类癌症患者样本进行经验性表征，目标是建立一个高度预测人类癌细胞行为的模型，这将从根本上改变我们目前对癌症转移机制的理解。将对来自人类癌症患者的一组连贯的样本进行广泛的经验测量和分析。随着时间的推移，样本将由来自原发肿瘤的细胞、局部转移的细胞和循环肿瘤细胞(CTCs)组成，所有这些都来自同一患者。此外，第二批样本将由来自一大批患者的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，并提供上皮癌空间和时间维度上的变量和相关性。这三个研究项目(RP)是：RP1细胞物理学，确定癌细胞的物理和机械性质；RP2拓扑，测量癌细胞的拓扑、形态和旅行群体策略；以及RP3动态组学，表征癌细胞的基因组学和转录组学。有了深度、广度和保真度的评估，测量将通过对其他参数的分析来实现，包括标准的病理和临床患者信息。这种广泛的数据融合主要基于物理调查和数学理论，但受到战略患者抽样和临床信息的影响，将通过高级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性模拟，这将彻底改变我们对转移的理解。4DB中心还将向新一代癌症物理学家传播信息、教育和培训，这一代人将利用物理学的力量征服癌症问题。

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.