title: Therapeutic implications from sensitivity analysis of tumor angiogenesis models.
abstract: Anti-angiogenic cancer treatments induce tumor starvation and regression by targeting the tumor vasculature that delivers oxygen and nutrients. Mathematical models prove valuable tools to study the proof-of-concept, efficacy and underlying mechanisms of such treatment approaches. The effects of parameter value uncertainties for two models of tumor development under angiogenic signaling and anti-angiogenic treatment are studied. Data fitting is performed to compare predictions of both models and to obtain nominal parameter values for sensitivity analysis. Sensitivity analysis reveals that the success of different cancer treatments depends on tumor size and tumor intrinsic parameters. In particular, we show that tumors with ample vascular support can be successfully targeted with conventional cytotoxic treatments. On the other hand, tumors with curtailed vascular support are not limited by their growth rate and therefore interruption of neovascularization emerges as the most promising treatment target.
authors.affiliation: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, Boston, Massachusetts, United States of America; College of Inter-faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, Warsaw, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Poleszczuk
authors.affiliation: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Philip
authors.initials: P
authors.lastname: Hahnfeldt
authors.affiliation: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Heiko
authors.initials: H
authors.lastname: Enderling
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000068258:Bevacizumab / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab