(160d) Modeling the Effect of Chemotaxis In Glioblastoma Tumor Progression

The American Cancer Society estimates that 21,810 patients will be diagnosed with brain and other central nervous system cancers and 13,070 patients with this disease will die in the US during 2008. The most common and lethal form of this disease is glioblastoma multiforme (grade IV in the World Health Organization classification). Glioblastomas are intracranial neoplasms with uncontrolled proliferation, generally with a necrotic core, marked angiogenesis, bizarre infiltrating ability and high resistance to radio- and chemo-therapy. In developing therapeutics for this disease, it is critical to understand the intricate relationship between the many biological processes that take place during tumor progression.

We present 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. Specifically, we focus on the temporal-spatial distribution of key biochemical cues (e.g., nutrient, growth factors) and the intracellular signaling pathways (e.g., PI3K-Akt and MAPK pathways) underlying the tumor growth, tumor cell migration and angiogenesis processes. We employ the model to explore the effect of possible migration mechanisms on the growth and invasion properties of the tumor. Simulation results show that the model is able to recapitulate in silico the morphology of brain tumors. We believe that the proposed modeling base (after further development and refinement) could ultimately help identify spatio-temporal dependent targets for tumor suppression that may otherwise remain concealed.