Fig. 5. Combined targeting of VEGFR2 and EGFR suppresses tumour growth and vasectasia.

a Schematic representation of the treatment with EGFR and VEGFR-2 inhibitors. Dacomitinib was administered by gavage at 15 mg/kg for 5 consecutive days followed by a 2-day break, while DC-101 was injected intra-peritoneally at 20 mg/kg, twice a week. Lactate and IgG at corresponding concentrations were injected in parallel, as placebo controls. The mice were treated with single agents alone, or in combination; b Survival curves of mice harbouring mesenchymal glioma stem cell xenografts (GSC83) subjected to a combination therapy targeting VEGF and EGFR pathways. Kaplan-Meier plot depicts groups of mice treated with placebo (IgG + lactate), DC-101 or Dacomitinib alone or with combination therapy of DC-101+ Dacomitinib (n = 5 independent experiments; two-tailed paired t test; P = 0.0075–0.000051 and 0.0000223); c Representative images of immunofluorescent staining for CD31 reveals the impact of therapy on vascular patterns. d Quantification of vessel size distribution based on CD31 staining. Blood vessels in mice treated with placebo (IgG + lactate) and single treatment with DC-101 present enlarged lumen compared to a mean vessel diameter of GSC83 (83) tumours treated with Dacomitinib and combination therapy of DC-101+ Dacomitinib (n = 5 independent experiments; two-tailed paired t test; P = 4.99⁻⁰⁸ and 2.18⁻¹⁰); e Quantification of microvascular density following CD31 staining. Microvascular density was increased in tumours treated with Dacomitinib and combination therapy of DC-101+ Dacomitinib as measured by vessel numbers per high power field (hpf; n = 5 independent experiments; two-tailed paired t test; P = 7.92⁻⁰⁶ and 1.45⁻⁰⁵). Data were presented as means ± SD. Significance: **p < 0.01, ***p < 0.001, ****p < 0.0001 treated group versus untreated control group; Source data are provided as a Source Data file.