Computational modeling of therapy on pancreatic cancer in its early stages

被引:0
作者
Jiao Chen
Daphne Weihs
Fred J. Vermolen
机构
[1] Delft University of Technology,Delft Institute of Applied Mathematics
[2] Technion-Israel Institute of Technology,Faculty of Biomedical Engineering
来源
Biomechanics and Modeling in Mechanobiology | 2020年 / 19卷
关键词
Mathematical modeling; Pancreatic cancer; Cancer therapy; Cell migration; Monte Carlo simulations;
D O I
暂无
中图分类号
学科分类号
摘要
More than eighty percent of pancreatic cancer involves ductal adenocarcinoma with an abundant desmoplastic extracellular matrix surrounding the solid tumor entity. This aberrant tumor microenvironment facilitates a strong resistance of pancreatic cancer to medication. Although various therapeutic strategies have been reported to be effective in mice with pancreatic cancer, they still need to be tested quantitatively in wider animal-based experiments before being applied as therapies. To aid the design of experiments, we develop a cell-based mathematical model to describe cancer progression under therapy with a specific application to pancreatic cancer. The displacement of cells is simulated by solving a large system of stochastic differential equations with the Euler–Maruyama method. We consider treatment with the PEGylated drug PEGPH20 that breaks down hyaluronan in desmoplastic stroma followed by administration of the chemotherapy drug gemcitabine to inhibit the proliferation of cancer cells. Modeling the effects of PEGPH20 + gemcitabine concentrations is based on Green’s fundamental solutions of the reaction–diffusion equation. Moreover, Monte Carlo simulations are performed to quantitatively investigate uncertainties in the input parameters as well as predictions for the likelihood of success of cancer therapy. Our simplified model is able to simulate cancer progression and evaluate treatments to inhibit the progression of cancer.
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页码:427 / 444
页数:17
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