Therapeutic implications from sensitivity analysis of tumor angiogenesis models

PloS One
Jan PoleszczukHeiko 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.

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Citations

Jan 31, 2016·Journal of Theoretical Biology·Luis Soto-Ortiz, Stacey D Finley
Dec 10, 2015·Current Problems in Cancer·Rachel Walker, Heiko Enderling
Aug 23, 2016·Journal of Molecular and Cellular Cardiology·Pei-Chi YangColleen E Clancy
May 12, 2018·Molecular Medicine Reports·Dongwei DaiBo Hong
Jul 25, 2019·Bulletin of Mathematical Biology·Renee Brady, Heiko Enderling
Jun 28, 2018·Bulletin of Mathematical Biology·Yixuan HeDorothy I Wallace
Jul 6, 2019·Molecular Biology Reports·Mariia ZadorozhnaDomenica Mangieri
Sep 12, 2018·International Journal of Molecular Sciences·Ruijing HuangJialiang Hu

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Software Mentioned

MATLAB

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