The tumor as an organ: comprehensive spatial and temporal modeling of the tumor and its microenvironment

BMC Bioinformatics. 2016 Aug 24;17(1):317. doi: 10.1186/s12859-016-1168-5.

Abstract

Background: Research related to cancer is vast, and continues in earnest in many directions. Due to the complexity of cancer, a better understanding of tumor growth dynamics can be gleaned from a dynamic computational model. We present a comprehensive, fully executable, spatial and temporal 3D computational model of the development of a cancerous tumor together with its environment.

Results: The model was created using Statecharts, which were then connected to an interactive animation front-end that we developed especially for this work, making it possible to visualize on the fly the on-going events of the system's execution, as well as the effect of various input parameters. We were thus able to gain a better understanding of, e.g., how different amounts or thresholds of oxygen and VEGF (vascular endothelial growth factor) affect the progression of the tumor. We found that the tumor has a critical turning point, where it either dies or recovers. If minimum conditions are met at that time, it eventually develops into a full, active, growing tumor, regardless of the actual amount; otherwise it dies.

Conclusions: This brings us to the conclusion that the tumor is in fact a very robust system: changing initial values of VEGF and oxygen can increase the time it takes to become fully developed, but will not necessarily completely eliminate it.

Keywords: Biological systems; Computational models; Statecharts; Tumor and its microenvironment; Visualization.

MeSH terms

  • Computer Simulation*
  • Disease Progression
  • Humans
  • Models, Biological
  • Neoplasms / blood supply
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic
  • Oxygen / metabolism
  • Tumor Microenvironment*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Oxygen