Computational modeling of therapy on pancreatic cancer in its early stages

Abstract

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.

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

“…Mathematical modeling and computational analysis are actively being pursued in several aspects of oncology to personalize and improve therapeutic outcomes (e.g., Ibrahim-Hashim et al, 2017 ). In particular, tissue structure and transport in liver ( Rani et al, 2006 ; Hoehme et al, 2007 ; Campbell et al, 2008 ; Hoehme et al, 2010 , 2017 , 2018 ; Holzhutter et al, 2012 ; Drasdo et al, 2014 ; Dutta-Moscato et al, 2014 ; Lettmann and Hardtke-Wolenski, 2014 ; Schliess et al, 2014 ; Siggers et al, 2014 ; Bethge et al, 2015 ; Ricken et al, 2015 ; Schwen et al, 2015 ; Nishii et al, 2016 ; Sluka et al, 2016 ; White et al, 2016 ; Friedman and Hao, 2017 ; Hudson et al, 2017 , 2019 ; Meyer et al, 2017 ; Fu et al, 2018 ; Mahlbacher et al, 2018 ; Clendenon et al, 2019 ; Van Liedekerke et al, 2020 ) as well as pancreas ( Haeno et al, 2012 ; Louzoun et al, 2014 ; Ng and Frieboes, 2017 , 2018 ; Roy and Finley, 2017 ; Yamamoto et al, 2017 ; Chen et al, 2020 ; Dogra et al, 2020b ) have been modeled. While numerous studies have simulated tumor growth and angiogenesis [see recent reviews and related work ( Cristini et al, 2008 ; Edelman et al, 2010 ; Lowengrub et al, 2010 ; Osborne et al, 2010 ; Rejniak and McCawley, 2010 ; Vineis et al, 2010 ; Andasari et al, 2011 ; Chaplain, 2011 ; Deisboeck et al, 2011 ; Frieboes et al, 2011 ; Michor et al, 2011 ; Rejniak and Anderson, 2011 ; Swanson et al, 2011 )] including metastatic conditions ( Campbell et al, 2008 ; Haeno et al, 2012 ; …”

A Cellular Automata Model of Oncolytic Virotherapy in Pancreatic Cancer

“…However, currently, viruses are not deemed as a useful means to stop or inhibit cancer since there is no effective way to control the virulence and retaining their replication capability in cancer cells (Kelly and Russell 2007). We have developed a cell-based model in pancreatic cancer at early stages (Chen et al 2018b), which is subsequently extended to therapy model in (Chen et al 2019). However, compared to classical treatments for pancreatic cancer like surgery, radiotherapy, chemotherapy, virotherapy has its own limitations, which needs further scientific assessment.…”

Digitally Fabricated and Naturally Augmented In Vitro Tissues

“…Hence, modeling tumor growth kinetics with continuum computation has become a topic of increasing interest. [101][102][103] Vascular and avascular growth are different phases of growth of solid tumors in vivo. [104] The initial avascular phase can be compared to 3D in vitro cultures in the labo-ratory, whereas the vascular phase involves the process of new blood vessel formation or angiogenesis, which is a core hallmark of cancer.…”