title: Progress Towards Computational 3-D Multicellular Systems Biology.
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.
authors.affiliation: Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA. Paul.Macklin@MathCancer.org.
authors.forename: Paul
authors.initials: P
authors.lastname: Macklin
authors.affiliation: Department of Bioengineering, University of Louisville, Louisville, KY, USA.
authors.forename: Hermann B
authors.initials: HB
authors.lastname: Frieboes
authors.affiliation: Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, OH, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sparks
authors.affiliation: Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Ahmadreza
authors.initials: A
authors.lastname: Ghaffarizadeh
authors.affiliation: Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Friedman
authors.affiliation: Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Electrical Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Edwin F
authors.initials: EF
authors.lastname: Juarez
authors.affiliation: Department of Electrical Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Edmond
authors.initials: E
authors.lastname: Jonckheere
authors.affiliation: Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Mumenthaler
mesh_terms: D003198:Computer Simulation; D042783:Endothelial Cells / Q000473:pathology / Q000648:ultrastructure; D045604:Extracellular Fluid / Q000000981:diagnostic imaging*; D006439:Hemodynamics; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000706:statistics & numerical data; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000473:pathology; D015203:Reproducibility of Results; D012984:Software; D049490:Systems Biology / Q000379:methods*; D059016:Tumor Microenvironment; D066253:Vascular Remodeling
keywords: Cancer microenvironment; Computational modeling; Multicellular systems biology; Tissue engineering