2020/09/01 by Giada Fiandaca, Marcello Delitala, Fiandaca, Giada +3 · 2 citations
Biochemistry, Genetics and Molecular Biology · Mathematics · #Cancer, Hypoxia, and Metabolism #FOS: Biological sciences #Mathematical Biology Tumor Growth #Microtubule and mitosis dynamics #Tissues and Organs (q-bio.TO)
paper · pdf · doi:10.48550/arxiv.2009.00251
openalex publication_date 2020/09/01 · openalex created_date 2022/07/25 · openalex updated_date 2026/07/28
Hypoxia and acidity act as environmental stressors promoting selection for\ncancer cells with a more aggressive phenotype. As a result, a deeper\ntheoretical understanding of the spatio-temporal processes that drive the\nadaptation of tumour cells to hypoxic and acidic microenvironments may open up\nnew avenues of research in oncology and cancer treatment. We present a\nmathematical model to study the influence of hypoxia and acidity on the\nevolutionary dynamics of cancer cells in vascularised tumours. The model is\nformulated as a system of partial integro-differential equations that describe\nthe phenotypic evolution of cancer cells in response to dynamic variations in\nthe spatial distribution of three abiotic factors that are key players in\ntumour metabolism: oxygen, glucose and lactate. The results of numerical\nsimulations of a calibrated version of the model based on real data\nrecapitulate the eco-evolutionary spatial dynamics of tumour cells and their\nadaptation to hypoxic and acidic microenvironments. Moreover, such results\ndemonstrate how nonlinear interactions between tumour cells and abiotic factors\ncan lead to the formation of environmental gradients which select for cells\nwith phenotypic characteristics that vary with distance from intra-tumour blood\nvessels, thus promoting the emergence of intra-tumour phenotypic heterogeneity.\nFinally, our theoretical findings reconcile the conclusions of earlier studies\nby showing that the order in which resistance to hypoxia and resistance to\nacidity arise in tumours depend on the ways in which oxygen and lactate act as\nenvironmental stressors in the evolutionary dynamics of cancer cells.\n