Therapeutic implications from sensitivity analysis of tumor angiogenesis models

PLoS One. 2015 Mar 18;10(3):e0120007. doi: 10.1371/journal.pone.0120007. eCollection 2015.

Abstract

Anti-angiogenic cancer treatments induce tumor starvation and regression by targeting the tumor vasculature that delivers oxygen and nutrients. Mathematical models prove valuable tools to study the proof-of-concept, efficacy and underlying mechanisms of such treatment approaches. The effects of parameter value uncertainties for two models of tumor development under angiogenic signaling and anti-angiogenic treatment are studied. Data fitting is performed to compare predictions of both models and to obtain nominal parameter values for sensitivity analysis. Sensitivity analysis reveals that the success of different cancer treatments depends on tumor size and tumor intrinsic parameters. In particular, we show that tumors with ample vascular support can be successfully targeted with conventional cytotoxic treatments. On the other hand, tumors with curtailed vascular support are not limited by their growth rate and therefore interruption of neovascularization emerges as the most promising treatment target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Bevacizumab / pharmacology
  • Bevacizumab / therapeutic use
  • Cell Proliferation / drug effects
  • Endothelial Cells / drug effects
  • Models, Biological*
  • Molecular Targeted Therapy
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic*
  • Treatment Outcome
  • Tumor Burden / drug effects

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab

Grant support

This project was supported by the Foundation for Polish Science (JP) and the National Cancer Institute under Award Number U54CA149233 (to Lynn Hlatky). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.