Modeling Tumor Blood Vessel Dynamics - Mathematical Methods and Models in Biomedicine - page 111

Modeling Tumor Blood Vessel Dynamics

Lance L. Munn, Christian Kunert, and J. Alex Tyrrell

1 Introduction

Tumor blood vessels are structurally abnormal and functionally inefficient, resulting
in incomplete perfusion of tumor vessel networks and nonuniform delivery of
chemotherapeutics to the tumor cells. Excessive production of the angiogenic
growth factor VEGF (vascular endothelial growth factor) contributes to tumor vessel
abnormalities, and many anti-VEGF therapies can cause remodeling or stabilization
of tumor blood vessels. This remodeling resembles the process of angioadaptation
previously studied in the context of normal physiology and ischemia. During
angioadaptation (also know as adaptive remodeling), endothelial cells respond to
blood forces to alter blood flow. Some segments dilate, while others contract,
eventually producing an efficient network. Although not well understood, it is likely
that adaptive remodeling depends on blood shear forces, transvascular pressure,
upstream signals transmitted along the endothelium as well as growth factors such
as VEGF. To provide an analytical framework for understanding these processes
in the context of tumor vasculature, we have developed a mathematical model,
supported by multiparameter imaging methodology, which incorporates the neces-
sary 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.
A better understanding of the mechanisms responsible for the network dynamics
may lead to novel approaches for treating tumors or other diseases involving
vascular pathologies.
Anti-angiognenic therapy induces structural and functional changes in tumor
vasculature, collectively known as vascular normalization [ 37 , 60 ], that can

L.L. Munn ( ) ￿ C. Kunert ￿ J. Alex Tyrrell
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
e-mail: [e-mail] ; [e-mail] ;
[e-mail]