VEGF Trap induces antiglioma effect at different stages of disease.
Pathological angiogenesis is a hallmark of cancer, specifically of glioblastomas, the most malignant and common primary brain tumor. Vascular endothelial growth factor (VEGF) is the key protein in the regulation of the hypervascular phenotype of primary malignant brain tumors. In this study, we tested VEGF Trap, a soluble decoy receptor for VEGF, in an intracranial glioma model. VEGF Trap was administered in short or prolonged schedules to animals bearing human gliomas at different stages of disease. Of importance, VEGF Trap treatment was efficacious in both initial and advanced phases of tumor development by significantly increasing overall survival. Furthermore, this effect was enhanced in animals treated with more prolonged regimens. In addition, we observed the emergence of a VEGF Trap-resistant phenotype characterized by tumor growth and increased invasiveness. Our results suggest that VEGF Trap will be effective in treating both patients with recurrent or progressive resectable glioblastoma and patients that have undergone extensive initial surgery. Finally, our results indicate that the clinical success of VEGF Trap may depend on a prolonged treatment in combined therapy aiming to simultaneously inhibit angiogenesis and tumor invasion.
Gomez-Manzano
Candelaria
C
Department of Neuro-Oncology, Unit 1002, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. cmanzano@mdanderson.org
Holash
Jocelyn
J
Fueyo
Juan
J
Xu
Jing
J
Conrad
Charles A
CA
Aldape
Kenneth D
KD
de Groot
John F
JF
Bekele
B Nebiyou
BN
Yung
W K Alfred
WK
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor