Developing an Agent-Based Drug Model to Investigate the Synergistic Effects of Drug Combinations.

The growth and survival of cancer cells are greatly related to their surrounding microenvironment. To understand the regulation under the impact of anti-cancer drugs and their synergistic effects, we have developed a multiscale agent-based model that can investigate the synergistic effects of drug combinations with three innovations. First, it explores the synergistic effects of drug combinations in a huge dose combinational space at the cell line level. Second, it can simulate the interaction between cells and their microenvironment. Third, it employs both local and global optimization algorithms to train the key parameters and validate the predictive power of the model by using experimental data. The research results indicate that our multicellular system can not only describe the interactions between the microenvironment and cells in detail, but also predict the synergistic effects of drug combinations.