TY - JOUR
T1 - Mathematical Modelling of Phenotypic Selection Within Solid Tumours
AU - Chaplain, Mark A. J.
AU - Lorenzi, Tommaso
AU - LORZ, ALEXANDER
AU - Venkataraman, Chandrasekhar
N1 - KAUST Repository Item: Exported on 2023-01-26
Acknowledged KAUST grant number(s): BAS/1/1648-01-01, BAS/1/1648-01-02
Acknowledgements: CV wishes to acknowledge partial support from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642866. AL was supported by King Abdullah University of Science and Technology (KAUST) baseline and start-up funds (BAS/1/1648-01-01 and BAS/1/1648-01-02). MAJC gratefully acknowledges support of EPSRC grant no. EP/N014642/1.
PY - 2019/1/5
Y1 - 2019/1/5
N2 - We present a space- and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silico the role played by the spatial distribution of oxygen and therapeutic agents in mediating phenotypic selection of cancer cells. Numerical simulations are performed on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography. Our modelling extends our previous work in the area through the inclusion of multiple therapeutic agents, one that is cytostatic, whilst the other is cytotoxic. In agreement with our previous work, the results show that spatial inhomogeneities in oxygen and therapeutic agent concentrations, which emerge spontaneously in solid tumours, can promote the creation of distinct local niches and lead to the selection of different phenotypic variants within the same tumour. A novel conclusion we infer from the simulations and analysis is that, for the same total dose, therapeutic protocols based on a combination of cytotoxic and cytostatic agents can be more effective than therapeutic protocols relying solely on cytotoxic agents in reducing the number of viable cancer cells.
AB - We present a space- and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silico the role played by the spatial distribution of oxygen and therapeutic agents in mediating phenotypic selection of cancer cells. Numerical simulations are performed on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography. Our modelling extends our previous work in the area through the inclusion of multiple therapeutic agents, one that is cytostatic, whilst the other is cytotoxic. In agreement with our previous work, the results show that spatial inhomogeneities in oxygen and therapeutic agent concentrations, which emerge spontaneously in solid tumours, can promote the creation of distinct local niches and lead to the selection of different phenotypic variants within the same tumour. A novel conclusion we infer from the simulations and analysis is that, for the same total dose, therapeutic protocols based on a combination of cytotoxic and cytostatic agents can be more effective than therapeutic protocols relying solely on cytotoxic agents in reducing the number of viable cancer cells.
UR - http://hdl.handle.net/10754/631653
UR - http://link.springer.com/chapter/10.1007/978-3-319-96415-7_20
UR - http://www.scopus.com/inward/record.url?scp=85060060667&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-96415-7_20
DO - 10.1007/978-3-319-96415-7_20
M3 - Article
SN - 1439-7358
VL - 126
SP - 237
EP - 245
JO - Numerical Mathematics and Advanced Applications ENUMATH 2017
JF - Numerical Mathematics and Advanced Applications ENUMATH 2017
ER -
