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A spatial model of tumor-host interaction: Application of chemotherapy

1. Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455
2. Niels Bohr Institute, Center for Models of Life, Blegdamsvej 17, 2100 Copenhagen
3. Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232
4. Department of Chemistry, Vanderbilt University, Nashville, TN 37235
5. Department of Surgical Research, Beckman Research Institute of City of Hope, Duarte, CA 91010
6. Department of Mathematics, University of Iowa, Iowa City, IA 52242
7. Department of Applied Mathematics and Department of Pathology, University of Washington, Seattle, WA 98195
8. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232
9. H. Lee Moffitt Cancer Center & Research Institute, Integrated Mathematical Oncology, 12902 Magnolia Drive, Tampa, FL 33612

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.
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Keywords tumor invasion; anti-angiogenic therapy; hypoxia; chemotherapy; mathematical modeling.

Citation: Peter Hinow, Philip Gerlee, Lisa J. McCawley, Vito Quaranta, Madalina Ciobanu, Shizhen Wang, Jason M. Graham, Bruce P. Ayati, Jonathan Claridge, Kristin R. Swanson, Mary Loveless, Alexander R. A. Anderson. A spatial model of tumor-host interaction: Application of chemotherapy. Mathematical Biosciences and Engineering, 2009, 6(3): 521-546. doi: 10.3934/mbe.2009.6.521


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