Modeling Structural and Functional Adaptation of Tumor Vessel Networks During Antiangiogenic Therapy

  • Lance L. Munn
  • Walid Kamoun
  • Michael Dupin
  • James Alex Tyrrell
Chapter

Abstract

In many physiological processes, endothelial cells respond to blood forces, re-organizing locally through a process of adaptation to alter blood flow. Some segments dilate, while others are pruned, and eventually, a stable configuration is reached. In contrast, tumor blood vessels are chronically immature and inefficient, unable to achieve optimum perfusion throughout the network. It is thought that the angiogenic growth factor vascular endothelial growth factor (VEGF) contributes to this inefficiency, and indeed, many anti-VEGF therapies can cause maturation or stabilization of tumor blood vessels through a process resembling adaptive remodeling. Unfortunately very little is known about how adaptive remodeling affects the distribution of blood flow and the transport of nutrients and drugs into the tumor. In general, remodeling depends on blood shear forces, transvascular pressure as well as growth factors such as VEGF. To provide an analytical framework for understanding this process, we have developed a mathematical model, supported by multiparameter imaging methodology, that incorporates the necessary elements for predicting the transport of nutrients and drugs throughout tumor vessels and tissue, as well as the adaptive remodeling of the blood vessel network.

Keywords

Permeability Migration Convection Ischemia Tyrosine 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Lance L. Munn
    • 1
  • Walid Kamoun
    • 1
  • Michael Dupin
    • 1
  • James Alex Tyrrell
    • 1
  1. 1.Massachusetts General Hospital and Harvard Medical SchoolCharlestownUSA

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