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Therapeutic Implications from Sensitivity Analysis of Tumor Angiogenesis Models

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  • Jan Poleszczuk
  • Philip Hahnfeldt
  • Heiko Enderling

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.

Suggested Citation

  • Jan Poleszczuk & Philip Hahnfeldt & Heiko Enderling, 2015. "Therapeutic Implications from Sensitivity Analysis of Tumor Angiogenesis Models," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-10, March.
    • Handle: RePEc:plo:pone00:0120007
    DOI: 10.1371/journal.pone.0120007
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    Cited by:

    1. Dharma Raj Khatiwada & Miana Wallace, 2023. "Testing Doses and Treatment Timelines of Anti-Angiogenic Drug Bevacizumab Numerically as a Single-Agent for the Treatment of Ovarian Cancer," Mathematics, MDPI, vol. 11(2), pages 1-6, January.
    2. Dávid Csercsik & Levente Kovács, 2019. "Dynamic Modeling of the Angiogenic Switch and Its Inhibition by Bevacizumab," Complexity, Hindawi, vol. 2019, pages 1-18, January.

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