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VEGF Trap induces antiglioma effect at different stages of disease

Departments of Neuro-Oncology (C.G.-M., J.F., J.X., C.A.C., J.F.G., W.K.A.Y.), Pathology (K.D.A.), and Biostatistics and Applied Mathematics (B.N.B.), The University of Texas M. D. Anderson Cancer Center, Houston, TX; Regeneron Pharmaceuticals, Inc., Tarrytown, NY (J.H.); USA

Address correspondence to C. Gomez-Manzano, Department of Neuro-Oncology, Unit 1002, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA (cmanzano{at}mdanderson.org).

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.

Key Words: glioblastoma • therapy • VEGF • VEGF Trap

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