Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption.
Vascular endothelial growth factor (VEGF) is an important mediator of the intense 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 neutralizing anti-VEGF antibody, we demonstrate that inhibition of VEGF significantly prolongs survival in athymic rats inoculated in the basal ganglia with G55 human glioblastoma cells. Systemic anti-VEGF inhibition causes decreased tumor vascularity as well as a marked increase in tumor cell apoptosis in intracranial tumors. Although intracranial glioblastoma tumors grow more 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.
Rubenstein
J L
JL
Division of Hematology/Oncology, University of California, San Francisco, USA. jamesr@medicine.ucsf.edu
Kim
J
J
Ozawa
T
T
Zhang
M
M
Westphal
M
M
Deen
D F
DF
Shuman
M A
MA
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000628:therapy*; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D005909:Glioblastoma / Q000098:blood supply* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D011923:Rats, Nude; D015996:Survival Rate; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors