Multi-scale agent-based brain cancer modeling and prediction of TKI treatment response: Incorporating EGFR signaling pathway and angiogenesis

BMC Bioinformatics

Software

Le Zhang¹  Hua Tan²  Costas Strouthos³  Xiaobo Zhou⁴  Xiaoqiang Sun⁵  Jiguang Bao⁶ 

[1] College of Computer and Information Science, Southwest University, 400715, Chongqing, P R China;Department of Mathematical Sciences, Michigan Technological University, 49931, Houghton, MI, USA;College of Global Change and Earth System Science, Beijing normal University, 100875, Beijing, P R China;Computation-based Science and Technology Research Center, The Cyprus Institute, 1645, Nicosia, Cyprus;Department of Radiology, The Methodist Hospital Research Institute, Weil Cornell Medical College, 77030, Houston, TX, USA;Department of Radiology, The Methodist Hospital Research Institute, Weil Cornell Medical College, 77030, Houston, TX, USA;School of Mathematical Sciences, Beijing Normal University, 100875, Beijing, P R China;School of Mathematical Sciences, Beijing Normal University, 100875, Beijing, P R China;

关键词: Multi-scale;    Agent-based modeling;    EGFR signaling pathway;    Angiogenesis;    TKI treatment;   

DOI  :  10.1186/1471-2105-13-218

 received in 2012-04-04, accepted in 2012-08-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe epidermal growth factor receptor (EGFR) signaling pathway and angiogenesis in brain cancer act as an engine for tumor initiation, expansion and response to therapy. Since the existing literature does not have any models that investigate the impact of both angiogenesis and molecular signaling pathways on treatment, we propose a novel multi-scale, agent-based computational model that includes both angiogenesis and EGFR modules to study the response of brain cancer under tyrosine kinase inhibitors (TKIs) treatment.ResultsThe novel angiogenesis module integrated into the agent-based tumor model is based on a set of reaction–diffusion equations that describe the spatio-temporal evolution of the distributions of micro-environmental factors such as glucose, oxygen, TGFα, VEGF and fibronectin. These molecular species regulate tumor growth during angiogenesis. Each tumor cell is equipped with an EGFR signaling pathway linked to a cell-cycle pathway to determine its phenotype. EGFR TKIs are delivered through the blood vessels of tumor microvasculature and the response to treatment is studied.ConclusionsOur simulations demonstrated that entire tumor growth profile is a collective behaviour of cells regulated by the EGFR signaling pathway and the cell cycle. We also found that angiogenesis has a dual effect under TKI treatment: on one hand, through neo-vasculature TKIs are delivered to decrease tumor invasion; on the other hand, the neo-vasculature can transport glucose and oxygen to tumor cells to maintain their metabolism, which results in an increase of cell survival rate in the late simulation stages.

【 授权许可】

Unknown   
© Sun et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.