(373a) Multi-Scale Modeling of Tumor Growth and Vasculature Remodeling

Authors: 
Vital-Lopez, F. G. - Presenter, The Pennsylvania State University
Armaou, A. - Presenter, Pennsylvania State University
Hutnik, M. - Presenter, The Angiogenesis Foundation


The American Cancer Society estimates that 22,070 patients will be diagnosed with brain and other central nervous system cancers and 12,970 patients with this disease will die in the US during 2009. Glioblastomas, the most common and lethal of these diseases, are intracranial neoplasms with uncontrolled proliferation, generally with a necrotic core, marked angiogenesis, bizarre infiltrating ability and highly resistance to radio/chemotherapy. In previous efforts, we developed a mathematical agent-based model that describes the progression of a brain tumor by capturing the interplay between processes occurring at the intracellular and tissue levels [1]. We used the model to explore the effect of possible migration mechanisms on the growth and invasion properties of the tumor. In this work we extend the model by describing the vasculature using a more realistic topology as well as accounting for tumor-induced vasculature remodeling processes. In addition, we added to the intracellular model signaling pathways regulating tumor cell migration (i.e., PLC pathway), resistance to apoptosis (i.e., PI3K/Akt pathway) and response to hypoxia (i.e., HIF-1 signaling). Finally, we described the spatio-temporal distribution of anti-tumor and/or anti-angiogenic agents. The ultimate goal is that this modeling base will ultimately lead to an efficient approach to provide insights regarding the performance of promising drugs for tumor suppression.

[1] F. G. Vital-Lopez, A. Armaou, M. Hutnik and C. D. Maranas, Modeling the effect of chemotaxis in glioblastoma tumor progression, (Submitted).