The goal of this project is to investigate the role of the pathological architecture of tumor vasculature as an obstacle to effective treatment of tumors by chemotherapy and radiotherapy. A computer model of vascular growth patterns, and flow and transport characteristics will be used in conjunction with existing experimental data obtained from human tumors grown in immunodeficient mice to determine the extent to which tumor blood flow behaves like a percolation network. Structural data taken from intravital microscopy of tumors grown in mice will be used as a basis for developing a computer simulation of the vascular growth processes that lead to the seemingly chaotic architecture of tumor vasculature. Predictions of fluid flow behavior, and the spatial and temporal distribution of diffusible substances such as drugs and oxygen will be made. These predictions will then be compared to data obtained from experimental tumors. Preliminary studies show that a percolation model of tumor vasculature is promising as a tool for predicting the size and scale of avascular spaces in tumors and, relative to normal tissues, the greater range of tracer residence times in the blood and the increased spatial heterogeneity of the blood perfusion. The results of this study may help to better explain the existing clinical difficulties in delivering blood-borne treatment to solid tumors, and also to suggest new methods of delivering blood-borne therapies or making modifications to the tumor vasculature in ways that would aid treatment.
| Baish, James W; Stylianopoulos, Triantafyllos; Lanning, Ryan M et al. (2011) Scaling rules for diffusive drug delivery in tumor and normal tissues. Proc Natl Acad Sci U S A 108:1799-803 |
| Baish, J W; Jain, R K (2000) Fractals and cancer. Cancer Res 60:3683-8 |
| Gazit, Y; Baish, J W; Safabakhsh, N et al. (1997) Fractal characteristics of tumor vascular architecture during tumor growth and regression. Microcirculation 4:395-402 |
