The Onko3D team aims at developing an in-silico 3-D cell proliferation model in order to investigate possible treatments of tumors. To do so, we are developing a simulator based on three interdependent components:
1/ A behavioral engine, that simulates the behavior of cells (healthy or cancerous): based on checkpoints instead of phases, the behavioral engine takes into account internal and external stimuli (lack of nutriments, drugs, etc.) and its impacts on the cell cycle regulation. The 2-D proliferation of different cell lineages has been successfully simulated and the results of the simulation show a convergence between simulations and their equivalent in-vitro biological experiments.
2/ A simplified biophysics engine, which simulates the physical interactions between cells: this physics engine, inspired from the beam theory makes the simulation step up to the third dimension within a continuous environment while keeping a reasonable computation cost. It simulates the collision and adhesion between cells as well as membrane deformation.
3/ A simplified hydrodynamic model that aims at simulating the diffusion of molecular components within the environment and its penetration in a cell aggregate (more particularly in a 3-D spheroid). We want the simulator to be able to simulate a local lack of nutriment, the diffusion of drug in a spheroid, etc…
We hope this work will open new perspectives concerning therapeutic strategies: it could be used to predict the impact of preclinical molecules before any in-vitro or in-vivo experience. The idea is to automatically discover optimal treatment protocols in order to efficiently use the drug. Once discovered in-silico, the treatment can then be tested in-vitro and/or in-vivo to be validated. Using the simulator might strongly reduce the time and cost effort necessary to validate a treatment.
