Anti-VEGF antibody treatment of glioblastoma prolongs survival but resultsin increased vascular cooption

Vascular endothelial growth factor (VEGF) is an important mediator of the i ntense angiogenesis which is characteristic of glioblastoma, While genetic manipulation of VEGF/VEGF receptor expression has previously been shown to inhibit glioblastoma growth, to date, no study has examined the efficacy of pharmacologic blockade of VEGF activity as a means to inhibit intracranial growth of human glioblastoma, Using intraperitoneal administration of a ne utralizing anti-VEGF antibody, we demonstrate that inhibition of VEGF signi ficantly prolongs survival in athymic rats inoculated in the basal ganglia with G55 human glioblastoma cells. Systemic anti-VEGF inhibition causes dec reased tumor vascularity as well as a marked increase in tumor cell apoptos is in intracranial tumors. Although intracranial glioblastoma tumors grow m ore slowly as a consequence of anti-VEGF treatment, the histologic pattern of growth suggests that these tumors adapt to inhibition of angiogenesis by increased infiltration and cooption of the host vasculature.