A spatial model of tumor-host interaction: application of chemotherapy.
In this paper we consider chemotherapy in a spatial model of tumor growth. The model, which is of reaction-diffusion type, takes into account the complex interactions between the tumor and surrounding stromal cells by including densities of endothelial cells and the extra-cellular matrix. When no treatment is applied the model reproduces the typical dynamics of early tumor growth. The initially avascular tumor reaches a diffusion limited size of the order of millimeters and initiates angiogenesis through the release of vascular endothelial growth factor (VEGF) secreted by hypoxic cells in the core of the tumor. This stimulates endothelial cells to migrate towards the tumor and establishes a nutrient supply sufficient for sustained invasion. To this model we apply cytostatic treatment in the form of a VEGF-inhibitor, which reduces the proliferation and chemotaxis of endothelial cells. This treatment has the capability to reduce tumor mass, but more importantly, we were able to determine that inhibition of endothelial cell proliferation is the more important of the two cellular functions targeted by the drug. Further, we considered the application of a cytotoxic drug that targets proliferating tumor cells. The drug was treated as a diffusible substance entering the tissue from the blood vessels. Our results show that depending on the characteristics of the drug it can either reduce the tumor mass significantly or in fact accelerate the growth rate of the tumor. This result seems to be due to complicated interplay between the stromal and tumor cell types and highlights the importance of considering chemotherapy in a spatial context.
Hinow
Peter
P
Institute for Mathematics and its Applications, University of Minnesota, Minneapolis, MN 55455, USA. hinow@ima.umn.edu
Gerlee
Philip
P
McCawley
Lisa J
LJ
Quaranta
Vito
V
Ciobanu
Madalina
M
Wang
Shizhen
S
Graham
Jason M
JM
Ayati
Bruce P
BP
Claridge
Jonathan
J
Swanson
Kristin R
KR
Loveless
Mary
M
Anderson
Alexander R A
AR
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003198:Computer Simulation; D000077143:Docetaxel; D042783:Endothelial Cells / Q000276:immunology; D006801:Humans; D018448:Models, Immunological; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000276:immunology*; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology*
D000970:Antineoplastic Agents; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel