An agent-based model for drug-radiation interactions in the tumour microenvironment: Hypoxia-activated prodrug SN30000 in multicellular tumour spheroids

by Xinjian Mao, Sarah McManaway, Jagdish K. Jaiswal, Priyanka B. Patel, William R. Wilson, Kevin O. Hicks, Gib Bogle

Multicellular tumour spheroids capture many characteristics of human tumour microenvironments, including hypoxia, and represent an experimentally tractablein vitro model for studying interactions between radiotherapy and anticancer drugs. However, interpreting spheroid data is challenging because of limited ability to observe cell fate within spheroids dynamically. To overcome this limitation, we have developed a hybrid continuum/agent-based model (ABM) for HCT116 tumour spheroids, parameterised using experimental models (monolayers and multilayers) in which reaction and diffusion can be measured directly. In the ABM, cell fate is simulated as a function of local oxygen, glucose and drug concentrations, determined by solving diffusion equations and intracellular reactions. The model is lattice-based, with cells occupying discrete locations on a 3D grid embedded within a coarser grid that encompasses the culture medium; separate solvers are employed for each grid. The generated concentration fields account for depletion in the medium and specify concentration-time profiles within the spheroid. Cell growth and survival are determined by intracellular oxygen and glucose concentrations, the latter based on direct measurement of glucose diffusion/reaction (in multilayers) for the first time. The ABM reproduces known features of spheroids including overall growth ra...

Source: PLoS Computational Biology - October 24, 2018 Category: Biology Authors: Xinjian Mao Source Type: research