Fig. 1. Overview of the model.

This figure schematically shows the three modules involved in the model and the interactions between them. The angiopoietin module accounts for the dynamics of Ang1, Ang2, Tie2, their corresponding complexes, and the phosphorylated form of the Tie2 receptor. The VEGF module accounts for the activation of VEGFR: upon binding of VEGF to its receptor, the VEGF/VEGFR complex forms a dimer. The VEGFRs within the dimer cross-phosphorylate their SH2 domains, thus acquiring tyrosine kinase activity. The cellular module accounts for the coupling between oxygen, cancer cells, endothelial cells, and cytokines dynamics. Continuous black lines with arrows refer to a positive feedback/influence of one agent on another, while dashed black lines with vertical bars refer to a negative feedback/influence. Red lines with vertical bars refer to the negative effects of PARP inhibitors on the indicated interaction. In the bracket, we indicate the variables used in the model to refer to the different agents (when it is different from the name of the population).