Model driven optimization of antiangiogenics + cytotoxics combination: application to breast cancer mice treated with bevacizumab + paclitaxel doublet leads to reduced tumor growth and fewer metastasis.

ABSTRACT: Bevacizumab is the first-in-class antiangiogenic drug and is almost always administrated in combination with cytotoxics. Reports have shown that bevacizumab could induce a transient phase of vascular normalization, thus ensuring a better drug delivery when cytotoxics administration is adjuvant. However, determining the best sequence remains challenging. We have developed a mathematical model describing the impact of antiangiogenics on tumor vasculature. A 3.4 days gap between bevacizumab and paclitaxel was first proposed by our model. To test its relevance, 84 mice were orthotopically xenografted with human MDA-231Luc+ refractory breast cancer cells. Two sets of experiments were performed, based upon different bevacizumab dosing (10 or 20 mg/kg) and inter-cycle intervals (7 or 10 days), co

SUBMITTER: Mollard S 

PROVIDER: S-EPMC5410287 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature