Searching a multicellular model to tame tumor-induced angiogenesis

Computational modeling has the potential to bridge the knowledge gap between the identification of cellular mechanisms altered in cancer and understanding development of the disease. A multicellular Glazier-Granier-Hogeweg (GGH)-based model that considers biologically realistic parameters of endothelial cells and the extracellular matrix was developed and used to explore how tumors induce angiogenesis. The effect on angiogenesis of modifying these parameters singly and in combination was examined in a massively parallel search to discover novel therapeutic approaches. A two phase search process was employed: First random restart hill climbing identified potentially valuable points within the search space, then multi-dimensional parameter sweeps were performed over the nearby region to further refine solution quality. Examples of combination therapies to block nutrient delivery to the tumor that were discovered in the search are presented. Multicellular modeling to identify potential cancer chemotherapies is a promising approach to reveal new targets for cancer drug development and testing.