Winter Interactive nanoBIO Workshop
1/5 Cancer Games/Glazier
Cancer Games: Interactive Simulation of the Effect of Resource Limitation on Cancer Somatic Evolution using nanoHUB CompuCell3D
James Glazier
January 5, 2021 2-3 pm EST
Abstract
During solid tumor progression, cells gradually acquire the ability to reproduce in ways deleterious to their host, to acquire nutrients and oxygen, to evade the host immune system and eventually, to remodel their environment, invade surrounding tissues and recapitulate their parent tumor organization in metastases. Progression is often regarded as an inevitable sequel of tumor initiation and its genetic and biomolecular bases are widely addressed. Less studied is somatic evolution within solid tumors, which combine rapid heritable mutation and strong selection. Tumor spread is determined by the behaviors of the small fraction of stem-like cells in the tumor, with higher stem-like fractions leading to more aggressive tumors and lower survival. Considering progression from an evolutionary perspective may help explain two apparent paradoxes: 1) Selection is intrinsically undirected, but results in deterministic progression. 2) Chemotherapies, surgery and raditation often result in substantial reduction of tumor mass, but ultimately lead to greater tumor mass and more invasive phenotypes. In this interactive mini-workshop we will use a very simple model of cancer somatic evolution and resource limitation based on one originally proposed by Heiko Enderling (see, e.g. Jan Poleszczuk, Philip Hahnfeldt, Heiko Enderling “Evolution and Phenotypic Selection of Cancer Stem Cells,” PLoS Computational Biology doi.org/10.1371/journal.pcbi.1004025 (2015)). In this game-theoretic model we have a single limiting resource, space to grow; cancer cells which can have either a stem-like (immortal) or somatic (limited number of cell divisions) phenotype, and undirected mutation in the rate of cell growth, fraction of stem cell divisions which give rise to two stem cells rather than a stem cell and a somatic cell (stemness) and the number of times a somatic cell can divide before dying (senescence). In this simple model the fraction of stem-like cells increases in time. We will study how this rate of increase depends on model parameters and show that partially effective treatments can actually result in rapid increase in the fraction of stem-like cells and hence worse outcomes. If time permits, we will also model the situation where the somatic cells protect the stem cells nearby from being killed by a chemotherapeutic agent.
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