1. Progress Towards Computational 3-D Multicellular Systems Biology.
- Author
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Macklin P, Frieboes HB, Sparks JL, Ghaffarizadeh A, Friedman SH, Juarez EF, Jonckheere E, and Mumenthaler SM
- Subjects
- Computer Simulation, Endothelial Cells pathology, Endothelial Cells ultrastructure, Hemodynamics, Humans, Imaging, Three-Dimensional statistics & numerical data, Neoplasms blood supply, Neoplasms pathology, Neoplasms ultrastructure, Neovascularization, Pathologic pathology, Reproducibility of Results, Software, Tumor Microenvironment, Extracellular Fluid diagnostic imaging, Models, Biological, Neoplasms diagnostic imaging, Neovascularization, Pathologic diagnostic imaging, Systems Biology methods, Vascular Remodeling
- Abstract
Tumors cannot be understood in isolation from their microenvironment. Tumor and stromal cells change phenotype based upon biochemical and biophysical inputs from their surroundings, even as they interact with and remodel the microenvironment. Cancer should be investigated as an adaptive, multicellular system in a dynamical microenvironment. Computational modeling offers the potential to detangle this complex system, but the modeling platform must ideally account for tumor heterogeneity, substrate and signaling factor biotransport, cell and tissue biophysics, tissue and vascular remodeling, microvascular and interstitial flow, and links between all these sub-systems. Such a platform should leverage high-throughput experimental data, while using open data standards for reproducibility. In this chapter, we review advances by our groups in these key areas, particularly in advanced models of tissue mechanics and interstitial flow, open source simulation software, high-throughput phenotypic screening, and multicellular data standards. In the future, we expect a transformation of computational cancer biology from individual groups modeling isolated parts of cancer, to coalitions of groups combining compatible tools to simulate the 3-D multicellular systems biology of cancer tissues.
- Published
- 2016
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