Modeling the emergence of phenotypic heterogeneity in vascularized tumors

DOI10.1137/19M1293971zbMATH Open1464.35382OpenAlexW3140640074MaRDI QIDQ4986537FDOQ4986537

Authors: Chiara Villa, T. Lorenzi, M. A. J. Chaplain 

Publication date: 27 April 2021

Published in: SIAM Journal on Applied Mathematics (Search for Journal in Brave)

Abstract: We present a mathematical study of the emergence of phenotypic heterogeneity in vascularised tumours. Our study is based on formal asymptotic analysis and numerical simulations of a system of non-local parabolic equations that describes the phenotypic evolution of tumour cells and their nonlinear dynamic interactions with the oxygen, which is released from the intratumoural vascular network. Numerical simulations are carried out both in the case of arbitrary distributions of intratumour blood vessels and in the case where the intratumoural vascular network is reconstructed from clinical images obtained using dynamic optical coherence tomography. The results obtained support a more in-depth theoretical understanding of the eco-evolutionary process which underpins the emergence of phenotypic heterogeneity in vascularised tumours. In particular, our results offer a theoretical basis for empirical evidence indicating that the phenotypic properties of cancer cells in vascularised tumours vary with the distance from the blood vessels, and establish a relation between the degree of tumour tissue vascularisation and the level of intratumour phenotypic heterogeneity.

Full work available at URL: https://arxiv.org/abs/1910.08566

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zbMATH Keywords

intratumor heterogeneityeco-evolutionary dynamicsnonlocal partial differential equationsmathematical oncologyvascularized tumors

Mathematics Subject Classification ID

Medical applications (general) (92C50) Population dynamics (general) (92D25) Asymptotic behavior of solutions to PDEs (35B40) Nonlinear parabolic equations (35K55) PDEs in connection with biology, chemistry and other natural sciences (35Q92) Cell biology (92C37)

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• Simulated ablation for detection of cells impacting paracrine signalling in histology analysis
• The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity
• A mathematical dissection of the adaptation of cell populations to fluctuating oxygen levels
• A phenotype-structured model to reproduce the avascular growth of a tumor and its interaction with the surrounding environment
• Mathematical modeling and quantitative analysis of phenotypic plasticity during tumor evolution based on single-cell data
• A mathematical study of the influence of hypoxia and acidity on the evolutionary dynamics of cancer
• Effective interface conditions for continuum mechanical models describing the invasion of multiple cell populations through thin membranes
• A particle model to reproduce collective migration and aggregation of cells with different phenotypes
• A simulation of parental and glycolytic tumor phenotype competition predicts observed responses to pH changes and increased glycolysis after anti-VEGF therapy

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