title: Computer Simulations of the Tumor Vasculature: Applications to Interstitial Fluid Flow, Drug Delivery, and Oxygen Supply.
abstract: Tumor vasculature, the blood vessel network supplying a growing tumor with nutrients such as oxygen or glucose, is in many respects different from the hierarchically organized arterio-venous blood vessel network in normal tissues. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature. Integrative models, based on detailed experimental data and physical laws, implement, in silico, the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. This chapter provides an overview over the current status of computer simulations of vascular remodeling during tumor growth including interstitial fluid flow, drug delivery, and oxygen supply within the tumor. The model predictions are compared with experimental and clinical data and a number of longstanding physiological paradigms about tumor vasculature and intratumoral solute transport are critically scrutinized.
authors.affiliation: Theoretical Physics, Saarland University, Campus E2 6, 66123, Saarbrücken, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Welter
authors.affiliation: Theoretical Physics, Saarland University, Campus E2 6, 66123, Saarbrücken, Germany. h.rieger@mx.uni-saarland.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Rieger
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D045604:Extracellular Fluid / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D051379:Mice; D008953:Models, Anatomic; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D010100:Oxygen
keywords: Angiogenesis; Computer simulation; Drug delivery; Interstitial fluid flow; Oxygenation; Tumor vascularization