Computer Simulations of the Tumor Vasculature: Applications to Interstitial Fluid Flow, Drug Delivery, and Oxygen Supply
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 format
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Computer Simulations of the Tumor Vasculature: Applications to Interstitial Fluid Flow, Drug Delivery, and Oxygen Supply Michael Welter and Heiko Rieger
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. Keywords
Tumor vascularization • Angiogenesis • Interstitial fluid flow • Drug delivery • Oxygenation • Computer simulation
M. Welter • H. Rieger () Theoretical Physics, Saarland University, Campus E2 6, 66123 Saarbrücken, Germany e-mail: [email protected]; [email protected]
3.1
Introduction
One of the hallmarks of cancer is angiogenesis, the formation of new blood vessels via sprouting, which fuels tumor growth with additional nutri-
© Springer International Publishing Switzerland 2016 K.A. Rejniak (ed.), Systems Biology of Tumor Microenvironment, Advances in Experimental Medicine and Biology 936, DOI 10.1007/978-3-319-42023-3_3
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ents [62]. Angiogenesis, vessel cooption (the inIn this chapter we review the current state of tegration of existing blood vessels into the tumor mathematical modeling and simulation of vasvasculature), dilatation, and vessel regression re- cularized tumor growth and discuss predictions model the healthy vascular network of the host made by our models for vascular morphology, into a tumor specific vasculature that is different drug delivery and oxygenation. It is organized as from the arterio-venous blood vessel network of follows: The first section provides an overview the host tissue [75]. Consequently blood flow, of the physiological basics of vascularized tuoxygen and nutrient supply, and interstitial fluid mor growth. It follows a section on obstac
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